NM_002528.7(NTHL1):c.246_247delinsAT (p.Asp83Tyr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 28, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002424861.3

Allele description [Variation Report for NM_002528.7(NTHL1):c.246_247delinsAT (p.Asp83Tyr)]

NM_002528.7(NTHL1):c.246_247delinsAT (p.Asp83Tyr)

Gene:

NTHL1:nth like DNA glycosylase 1 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_002528.7(NTHL1):c.246_247delinsAT (p.Asp83Tyr)

HGVS:

NC_000016.10:g.2046235_2046236delinsAT
NG_005895.1:g.1930_1931delinsAT
NG_008412.1:g.6631_6632delinsAT
NM_001318193.2:c.246_247delinsAT
NM_001318194.2:c.24+44_24+45delinsAT
NM_002528.7:c.246_247delinsATMANE SELECT
NP_001305122.2:p.Asp83Tyr
NP_002519.2:p.Asp83Tyr
LRG_1366t1:c.246_247delinsAT
LRG_1366:g.6631_6632delinsAT
LRG_1366p1:p.Asp83Tyr
LRG_487:g.1930_1931delinsAT
NC_000016.9:g.2096236_2096237delinsAT
NM_002528.5:c.270_271delGGinsAT
NM_002528.6:c.270_271delGGinsAT
NM_002528.6:c.270_271delinsAT

Protein change:

D83Y

Links:

dbSNP: rs1596222995

NCBI 1000 Genomes Browser:

rs1596222995

Molecular consequence:

NM_001318194.2:c.24+44_24+45delinsAT - intron variant - [Sequence Ontology: SO:0001627]
NM_001318193.2:c.246_247delinsAT - missense variant - [Sequence Ontology: SO:0001583]
NM_002528.7:c.246_247delinsAT - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

selenocysteine-specific translation elongation factor [Proteus sp. HMSC14B05]
selenocysteine-specific translation elongation factor [Proteus sp. HMSC14B05]
gi|1092500320|ref|WP_070487066.1|

Protein
Chain X, 26S proteasome non-ATPase regulatory subunit 11
Chain X, 26S proteasome non-ATPase regulatory subunit 11
gi|2234345974|pdb|7W3B|X

Protein
Chain G, Proteasome subunit alpha type-6
Chain G, Proteasome subunit alpha type-6
gi|2234345957|pdb|7W3B|G

Protein
Chain a, 26S proteasome non-ATPase regulatory subunit 13
Chain a, 26S proteasome non-ATPase regulatory subunit 13
gi|2234345977|pdb|7W3B|a

Protein
Chain m, Proteasome subunit alpha type-3
Chain m, Proteasome subunit alpha type-3
gi|2234345988|pdb|7W3B|m

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002741728	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 28, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002741728

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 28, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV002741728.3

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

Description

The c.270_271delGGinsAT variant (also known as p.D91Y), located in coding exon 2 of the NTHL1 gene, results from an in-frame deletion of GG and insertion of AT at nucleotide positions 270 to 271. This results in the substitution of the aspartic acid residue for a tyrosine residue at codon 91, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine