2-42682498-A-T

Position:

• chr2-42682498-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001330442.2(MTA3):​c.800A>T​(p.Glu267Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTA3 NM_001330442.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.04

Genes affected

MTA3 (HGNC:23784): (metastasis associated 1 family member 3) Predicted to enable histone deacetylase binding activity; transcription coactivator activity; and transcription corepressor activity. Involved in negative regulation of transcription, DNA-templated. Located in nucleoplasm. Part of NuRD complex. [provided by Alliance of Genome Resources, Apr 2022]

MTA3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTA3	NM_001330442.2	c.800A>T	p.Glu267Val	missense_variant	9/17	ENST00000405094.2	NP_001317371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTA3	ENST00000405094.2	c.800A>T	p.Glu267Val	missense_variant	9/17	5	NM_001330442.2	ENSP00000385823.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2024

The c.800A>T (p.E267V) alteration is located in exon 9 (coding exon 9) of the MTA3 gene. This alteration results from a A to T substitution at nucleotide position 800, causing the glutamic acid (E) at amino acid position 267 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T;.;T;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	.;D;D;D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.1	.;.;M;.;M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-6.0	D;D;D;D;D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Uncertain	0.037	D;D;D;D;D
Polyphen		0.95	P;P;P;P;.
Vest4		0.84
MutPred		0.62		Loss of disorder (P = 0.0089);Loss of disorder (P = 0.0089);.;.;.;
MVP		0.44
MPC		0.42
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.80
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-42909638;