NM_014168.4(METTL5):c.571_572del (p.Lys191fs) AND Intellectual developmental disorder, autosomal recessive 72

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 22, 2019
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000856617.1

Allele description [Variation Report for NM_014168.4(METTL5):c.571_572del (p.Lys191fs)]

NM_014168.4(METTL5):c.571_572del (p.Lys191fs)

Gene:

METTL5:methyltransferase 5, N6-adenosine [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q31.1

Genomic location:

Preferred name:

NM_014168.4(METTL5):c.571_572del (p.Lys191fs)

HGVS:

NC_000002.12:g.169812476_169812477del
NG_030640.1:g.18665_18666del
NM_001293186.2:c.571_572del
NM_001293187.2:c.571_572del
NM_014168.4:c.571_572delMANE SELECT
NP_001280115.1:p.Lys191fs
NP_001280116.1:p.Lys191fs
NP_054887.2:p.Lys191fs
NC_000002.11:g.170668986_170668987del
NM_014168.2:c.571_572del
NM_014168.2:c.571_572delAA

Protein change:

K191fs

Links:

OMIM: 618628.0002; dbSNP: rs1573965358

NCBI 1000 Genomes Browser:

rs1573965358

Molecular consequence:

NM_001293186.2:c.571_572del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293187.2:c.571_572del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014168.4:c.571_572del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Intellectual developmental disorder, autosomal recessive 72
Synonyms:: MENTAL RETARDATION, AUTOSOMAL RECESSIVE 72
Identifiers:: MONDO: MONDO:0032860; MedGen: C5231452; OMIM: 618665

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000999151	OMIM	no assertion criteria provided	Pathogenic (Nov 22, 2019)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000999151

OMIM

no assertion criteria provided

Pathogenic
(Nov 22, 2019)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Bi-allelic Variants in METTL5 Cause Autosomal-Recessive Intellectual Disability and Microcephaly.

Richard EM, Polla DL, Assir MZ, Contreras M, Shahzad M, Khan AA, Razzaq A, Akram J, Tarar MN, Blanpied TA, Ahmed ZM, Abou Jamra R, Wieczorek D, van Bokhoven H, Riazuddin S, Riazuddin S.

Am J Hum Genet. 2019 Oct 3;105(4):869-878. doi: 10.1016/j.ajhg.2019.09.007. Epub 2019 Sep 26.

PubMed [citation]

PMID:: 31564433
PMCID:: PMC6817559

Details of each submission

From OMIM, SCV000999151.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 brothers, born of consanguineous parents of Yemenite descent (family F47949), with autosomal recessive intellectual developmental disorder-72 (MRT72; 618665), Richard et al. (2019) identified a homozygous 2-bp deletion (c.571_572delAA, NM_014168.2) in the METTL5 gene, resulting in a frameshift and premature termination (Lys191ValfsTer10). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variant was not present in the gnomAD database. In vitro cellular studies in transfected COS7 and HEK293T cells showed that the mutation resulted in significantly decreased levels of the protein compared to wildtype, suggesting that the mutant protein was unstable and degraded by the proteosome.

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

Last Updated: Jun 23, 2024

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