NM_000518.5(HBB):c.16C>T (p.Pro6Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 2, 2021
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:: RCV000756240.18

Allele description [Variation Report for NM_000518.5(HBB):c.16C>T (p.Pro6Ser)]

NM_000518.5(HBB):c.16C>T (p.Pro6Ser)

Genes:

LOC106099062:HBB recombination region [Gene]
HBB:hemoglobin subunit beta [Gene - OMIM - HGNC]
LOC107133510:origin of replication at HBB [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_000518.5(HBB):c.16C>T (p.Pro6Ser)

Other names:

P5S; Hb Tyne

HGVS:

NC_000011.10:g.5227006G>A
NG_000007.3:g.70610C>T
NG_042296.1:g.537G>A
NG_046672.1:g.4941G>A
NG_059281.1:g.5066C>T
NM_000518.5:c.16C>TMANE SELECT
NP_000509.1:p.Pro6Ser
LRG_1232t1:c.16C>T
LRG_1232:g.5066C>T
LRG_1232p1:p.Pro6Ser
NC_000011.9:g.5248236G>A
NM_000518.4:c.16C>T

Protein change:

P6S; PRO5SER

Links:

HBVAR: 225; OMIM: 141900.0451; dbSNP: rs33912272

NCBI 1000 Genomes Browser:

rs33912272

Molecular consequence:

NM_000518.5:c.16C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000883988	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Uncertain significance (Nov 2, 2021)	germline	clinical testing	Citation Link,
SCV000889363	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Feb 2, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000883988

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)

Uncertain significance
(Nov 2, 2021)

germline

clinical testing

Citation Link,

SCV000889363

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Feb 2, 2018)

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	unknown	not provided	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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000883988.3

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

Description

The Hb Tyne variant (HBB: c.16C>T; p.Pro6Ser, also known as Pro5Ser when numbered from the mature protein; rs33912272) has been described in the heterozygous state in individuals with normal hematological findings (Pullon 2017, HbVar database and references therein). However, the variant has also been observed in an individual with a clinical diagnosis of beta thalassemia who also carried HbS (Keser 2010). The proline at codon 5 is weakly conserved, and computational programs (PolyPhen-2, SIFT) predict that this variant is tolerated, although isopropanol stability tests indicate this variant is slightly unstable (Pullon 2017, HbVar database). Due to limited information regarding this variant, its clinical significance cannot be determined with certainty. References: Link to HbVar database: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=225 Keser I et al. Abnormal hemoglobins associated with the beta-globin gene in Antalya province, Turkey. Turk J Med Sci. 2010;40(1): 127-131. Pullon BM and Brennan SO. Two familial cases of Hb Tyne confirm instability as cause of low expression. Thalassemia Reports. 2017; 7(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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000889363.2

#	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

Last Updated: Nov 3, 2024

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