NM_000518.5(HBB):c.108C>A (p.Tyr36Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 10, 2023
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:: RCV001800305.2

Allele description [Variation Report for NM_000518.5(HBB):c.108C>A (p.Tyr36Ter)]

NM_000518.5(HBB):c.108C>A (p.Tyr36Ter)

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.108C>A (p.Tyr36Ter)

Other names:

Y35*; CD 35 TAC>TAA

HGVS:

NC_000011.10:g.5226784G>T
NG_000007.3:g.70832C>A
NG_042296.1:g.315G>T
NG_046672.1:g.4719G>T
NG_059281.1:g.5288C>A
NM_000518.5:c.108C>AMANE SELECT
NP_000509.1:p.Tyr36Ter
LRG_1232t1:c.108C>A
HBB:c.108C>A
LRG_1232:g.5288C>A
LRG_1232p1:p.Tyr36Ter
NC_000011.9:g.5248014G>T
NM_000518.4:c.108C>A

Protein change:

Y36*; TYR35TER

Links:

HBVAR: 838; OMIM: 141900.0318; dbSNP: rs33982568

NCBI 1000 Genomes Browser:

rs33982568

Molecular consequence:

NM_000518.5:c.108C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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islet cell autoantigen 1 isoform a [Homo sapiens]
islet cell autoantigen 1 isoform a [Homo sapiens]
gi|1185542339|ref|NP_001337749.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002046602	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jan 27, 2021)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 27848919, 23590658, 9101288, 2393018, 2542242, 26467025
SCV004294105	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27848919, 23637309, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002046602

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jan 27, 2021)

unknown

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV004294105

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 10, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Prenatal and newborn screening for hemoglobinopathies.

Hoppe CC.

Int J Lab Hematol. 2013 Jun;35(3):297-305. doi: 10.1111/ijlh.12076. Review.

PubMed [citation]

PMID:: 23590658

beta-thalassemia mutations in Japanese and Koreans.

Ohba Y, Hattori Y, Harano T, Harano K, Fukumaki Y, Ideguchi H.

Hemoglobin. 1997 Mar;21(2):191-200. Review. No abstract available. Erratum in: Hemoglobin 1997 Jul;21(4):389.

PubMed [citation]

PMID:: 9101288

See all PubMed Citations (8)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002046602.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The nonsense variant causes the premature termination of HBB protein synthesis. In addition, it has been reported in individuals and families and associated with beta-0- thalassemia in the published literature (PMID: 2542242 (1989), 2393018 (1990), 9101288 (1997), 23590658 (2013), 27848919 (2016)).

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

From Invitae, SCV004294105.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 15408). This premature translational stop signal has been observed in individual(s) with Beta thalassemia (PMID: 27848919). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr36*) in the HBB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HBB are known to be pathogenic (PMID: 23637309).

#	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: Feb 20, 2024

ClinVar

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