NM_000546.6(TP53):c.659A>G (p.Tyr220Cys) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Jul 27, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000213055.38

Allele description [Variation Report for NM_000546.6(TP53):c.659A>G (p.Tyr220Cys)]

NM_000546.6(TP53):c.659A>G (p.Tyr220Cys)

Gene:

TP53:tumor protein p53 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.659A>G (p.Tyr220Cys)

Other names:

p.Y220C:TAT>TGT; NM_000546.6(TP53):c.659A>G

HGVS:

NC_000017.11:g.7674872T>C
NG_017013.2:g.17679A>G
NM_000546.6:c.659A>GMANE SELECT
NM_001126112.3:c.659A>G
NM_001126113.3:c.659A>G
NM_001126114.3:c.659A>G
NM_001126115.2:c.263A>G
NM_001126116.2:c.263A>G
NM_001126117.2:c.263A>G
NM_001126118.2:c.542A>G
NM_001276695.3:c.542A>G
NM_001276696.3:c.542A>G
NM_001276697.3:c.182A>G
NM_001276698.3:c.182A>G
NM_001276699.3:c.182A>G
NM_001276760.3:c.542A>G
NM_001276761.3:c.542A>G
NP_000537.3:p.Tyr220Cys
NP_000537.3:p.Tyr220Cys
NP_001119584.1:p.Tyr220Cys
NP_001119585.1:p.Tyr220Cys
NP_001119586.1:p.Tyr220Cys
NP_001119587.1:p.Tyr88Cys
NP_001119588.1:p.Tyr88Cys
NP_001119589.1:p.Tyr88Cys
NP_001119590.1:p.Tyr181Cys
NP_001263624.1:p.Tyr181Cys
NP_001263625.1:p.Tyr181Cys
NP_001263626.1:p.Tyr61Cys
NP_001263627.1:p.Tyr61Cys
NP_001263628.1:p.Tyr61Cys
NP_001263689.1:p.Tyr181Cys
NP_001263690.1:p.Tyr181Cys
LRG_321t1:c.659A>G
LRG_321:g.17679A>G
LRG_321p1:p.Tyr220Cys
NC_000017.10:g.7578190T>C
NM_000546.4:c.659A>G
NM_000546.5(TP53):c.659A>G
NM_000546.5:c.659A>G
P04637:p.Tyr220Cys
p.Y220C

Protein change:

Y181C

Links:

UniProtKB: P04637#VAR_005957; dbSNP: rs121912666

NCBI 1000 Genomes Browser:

rs121912666

Molecular consequence:

NM_000546.6:c.659A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.659A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.659A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.659A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.263A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.263A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.263A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.542A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.542A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.542A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.182A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.182A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.182A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.542A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.542A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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RecName: Full=Testis-specific Y-encoded-like protein 1; Short=TSPY-like protein ...
RecName: Full=Testis-specific Y-encoded-like protein 1; Short=TSPY-like protein 1
gi|209572711|sp|Q9H0U9.3|TSYL1_HUMA

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000149640	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 27, 2022)	germline	clinical testing	Citation Link,
SCV000700520	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Mar 2, 2017)	germline	clinical testing	Citation Link,
SCV000888669	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Aug 1, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001247047	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Feb 1, 2019)	germline	clinical testing	Citation Link,
SCV002022390	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 10, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000149640.17

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression activity (Kato 2003, Malcikova 2010, Monti 2011, Giacomelli 2018, Kotler 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23365691, 17015838, 22923379, 27470445, 27503952, 28091804, 28679691, 27322648, 29853601, 20407015, 26619011, 24487413, 20128691, 17606709, 24395441, 19367569, 24573247, 21343334, 18307025, 19101993, 8118819, 10432928, 15977174, 20028212, 20805372, 21761402, 23484829, 24702488, 27840695, 27714481, 23315175, 28861920, 29099488, 28369373, 28915717, 28980058, 28076841, 28818333, 29099487, 28643165, 29190505, 28948977, 29979965, 29702446, 30309854, 30032819, 23630318, 30079495, 30720243, 30630526, 31016814, 30840781, 15722483, 10713666, 9627118, 16861262, 15510160, 12826609, 24641375, 31105275, 33300245, 32994724, 32817165, 33087929, 30224644)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Eurofins Ntd Llc (ga), SCV000700520.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		2	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000888669.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001247047.24

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002022390.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 25, 2024

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