Variant chr14-105464683-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_004689.4(MTA1):c.1354G>A(p.Gly452Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,603,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

MTA1
NM_004689.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.64

Variant links:

Genes affected

MTA1 (HGNC:7410): (metastasis associated 1) This gene encodes a protein that was identified in a screen for genes expressed in metastatic cells, specifically, mammary adenocarcinoma cell lines. Expression of this gene has been correlated with the metastatic potential of at least two types of carcinomas although it is also expressed in many normal tissues. The role it plays in metastasis is unclear. It was initially thought to be the 70kD component of a nucleosome remodeling deacetylase complex, NuRD, but it is more likely that this component is a different but very similar protein. These two proteins are so closely related, though, that they share the same types of domains. These domains include two DNA binding domains, a dimerization domain, and a domain commonly found in proteins that methylate DNA. The profile and activity of this gene product suggest that it is involved in regulating transcription and that this may be accomplished by chromatin remodeling. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

MTA1 links:

MTA1 (HGNC:):

MTA1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26622638).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTA1	NM_004689.4 linkuse as main transcript	c.1354G>A	p.Gly452Ser	missense_variant	15/21	ENST00000331320.12	NP_004680.2	Q13330-1Q9BRL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTA1	ENST00000331320.12 linkuse as main transcript	c.1354G>A	p.Gly452Ser	missense_variant	15/21	1	NM_004689.4	ENSP00000333633.7		Q13330-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000248

AC:

AN:

241990

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132042

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000144

Gnomad NFE exome

AF:

0.00000926

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1451222

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

720270

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000386

Gnomad4 NFE exome

AF:

0.00000724

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000452

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000248

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2022

The c.1354G>A (p.G452S) alteration is located in exon 15 (coding exon 15) of the MTA1 gene. This alteration results from a G to A substitution at nucleotide position 1354, causing the glycine (G) at amino acid position 452 to be replaced by a serine (S). 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

0.069

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

T;T;.;.

Eigen

Benign

0.060

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.;.

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Benign

0.15

Sift

Benign

0.098

T;T;T;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.064

B;.;.;.

Vest4

0.54

MVP

0.64

MPC

0.53

ClinPred

0.67

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over