NM_017635.5(KMT5B):c.2434C>T (p.Arg812Ter) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 22, 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:: RCV004027176.1

Allele description [Variation Report for NM_017635.5(KMT5B):c.2434C>T (p.Arg812Ter)]

NM_017635.5(KMT5B):c.2434C>T (p.Arg812Ter)

Gene:

KMT5B:lysine methyltransferase 5B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_017635.5(KMT5B):c.2434C>T (p.Arg812Ter)

HGVS:

NC_000011.10:g.68157912G>A
NG_052873.1:g.60861C>T
NM_001300907.1:c.1918C>T
NM_001300908.2:c.1714C>T
NM_001369426.1:c.2434C>T
NM_001369428.1:c.1918C>T
NM_001369429.1:c.1918C>T
NM_001369430.1:c.1918C>T
NM_001369431.1:c.1918C>T
NM_001369432.1:c.1918C>T
NM_001369433.1:c.1918C>T
NM_017635.5:c.2434C>TMANE SELECT
NP_001287836.1:p.Arg640Ter
NP_001287837.1:p.Arg572Ter
NP_001356355.1:p.Arg812Ter
NP_001356357.1:p.Arg640Ter
NP_001356358.1:p.Arg640Ter
NP_001356359.1:p.Arg640Ter
NP_001356360.1:p.Arg640Ter
NP_001356361.1:p.Arg640Ter
NP_001356362.1:p.Arg640Ter
NP_060105.3:p.Arg812Ter
NC_000011.9:g.67925379G>A
NM_017635.3:c.2434C>T

Protein change:

R572*

Links:

dbSNP: rs1565212298

NCBI 1000 Genomes Browser:

rs1565212298

Molecular consequence:

NM_001300907.1:c.1918C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001300908.2:c.1714C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369426.1:c.2434C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369428.1:c.1918C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369429.1:c.1918C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369430.1:c.1918C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369431.1:c.1918C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369432.1:c.1918C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369433.1:c.1918C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_017635.5:c.2434C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

Recent activity

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Perca fluviatilis voucher Pf_M1, whole genome shotgun sequencing project
Perca fluviatilis voucher Pf_M1, whole genome shotgun sequencing project
gi|1802907429|gb|VHII00000000.1|VHI 0000

Nucleotide
NADH dehydrogenase subunit 4L (mitochondrion) [Perca fluviatilis]
NADH dehydrogenase subunit 4L (mitochondrion) [Perca fluviatilis]
gi|1802882662|gb|KAF1371393.1||gnl| HII|PFLUV_P0027900

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004896660	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Feb 22, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004896660

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Feb 22, 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, SCV004896660.1

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

Description

The c.2434C>T (p.R812*) alteration, located in exon 11 (coding exon 10) of the KMT5B gene, consists of a C to T substitution at nucleotide position 2434. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 812. This alteration occurs at the 3' terminus of the KMT5B gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 8.4% of the protein. However, premature stop codons are typically deleterious in nature, the impacted region is critical for protein function, and a significant portion of the protein is affected (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in one individual with seizures, autism, intellectual disability, and macrocephaly (External communication). Based on the available evidence, this alteration is classified as likely pathogenic.

#	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: May 7, 2024

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