2-42708026-A-G

Position:

• chr2-42708026-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330442.2(MTA3):​c.1274A>G​(p.Glu425Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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: 5.58

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16920406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTA3	NM_001330442.2	c.1274A>G	p.Glu425Gly	missense_variant	13/17	ENST00000405094.2	NP_001317371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTA3	ENST00000405094.2	c.1274A>G	p.Glu425Gly	missense_variant	13/17	5	NM_001330442.2	ENSP00000385823.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Aug 26, 2024

The c.1274A>G (p.E425G) alteration is located in exon 13 (coding exon 13) of the MTA3 gene. This alteration results from a A to G substitution at nucleotide position 1274, causing the glutamic acid (E) at amino acid position 425 to be replaced by a glycine (G). 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	Benign	0.11
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;T;.;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	.;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.1	.;.;M;.;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.062	T;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T
Polyphen		0.31	B;B;B;B;.
Vest4		0.18
MutPred		0.19		Loss of stability (P = 0.0322);Loss of stability (P = 0.0322);.;.;.;
MVP		0.10
MPC		0.32
ClinPred		0.86	D
GERP RS		6.0
Varity_R		0.14
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-42935166;