NM_001130823.3(DNMT1):c.289C>T (p.His97Tyr) AND Hereditary sensory neuropathy-deafness-dementia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 16, 2023
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:: RCV003528401.2

Allele description [Variation Report for NM_001130823.3(DNMT1):c.289C>T (p.His97Tyr)]

NM_001130823.3(DNMT1):c.289C>T (p.His97Tyr)

Gene:

DNMT1:DNA methyltransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_001130823.3(DNMT1):c.289C>T (p.His97Tyr)

HGVS:

NC_000019.10:g.10180506G>A
NG_028016.3:g.55781C>T
NM_001130823.3:c.289C>TMANE SELECT
NM_001318730.2:c.289C>T
NM_001318731.2:c.-75C>T
NM_001379.4:c.289C>T
NP_001124295.1:p.His97Tyr
NP_001124295.1:p.His97Tyr
NP_001305659.1:p.His97Tyr
NP_001370.1:p.His97Tyr
LRG_362t1:c.289C>T
LRG_362:g.55781C>T
LRG_362p1:p.His97Tyr
NC_000019.9:g.10291182G>A
NM_001130823.1:c.289C>T
NM_001379.2:c.289C>T

Protein change:

H97Y

Molecular consequence:

NM_001318731.2:c.-75C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001130823.3:c.289C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001318730.2:c.289C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379.4:c.289C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary sensory neuropathy-deafness-dementia syndrome
Synonyms:: HSN IE; NEUROPATHY, HEREDITARY SENSORY, WITH HEARING LOSS AND DEMENTIA; Hereditary sensory neuropathy type IE
Identifiers:: MONDO: MONDO:0013584; MedGen: C3279885; Orphanet: 456318; OMIM: 614116

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Treponema putidum strain OMZ 848 recombinase A (recA) gene, partial cds
Treponema putidum strain OMZ 848 recombinase A (recA) gene, partial cds
gi|392357760|gb|JN244665.1|

Nucleotide
Streptococcus pneumoniae strain SMRU1951, whole genome shotgun sequence
Streptococcus pneumoniae strain SMRU1951, whole genome shotgun sequence
gi|950865741|ref|NZ_CICI01000003.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004270159	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 16, 2023)	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

SCV004270159

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 16, 2023)

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004270159.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1797393). This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. This variant is present in population databases (rs753670606, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 97 of the DNMT1 protein (p.His97Tyr).

#	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

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