chr11-62593943-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004739.4(MTA2):​c.1939C>T​(p.Pro647Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

MTA2
NM_004739.4 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22
Variant links:
Genes affected
MTA2 (HGNC:7411): (metastasis associated 1 family member 2) This gene encodes a protein that has been identified as a component of NuRD, a nucleosome remodeling deacetylase complex identified in the nucleus of human cells. It shows a very broad expression pattern and is strongly expressed in many tissues. It may represent one member of a small gene family that encode different but related proteins involved either directly or indirectly in transcriptional regulation. Their indirect effects on transcriptional regulation may include chromatin remodeling. It is closely related to another member of this family, a protein that has been correlated with the metastatic potential of certain carcinomas. These two proteins are so closely related 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. One of the proteins known to be a target protein for this gene product is p53. Deacetylation of p53 is correlated with a loss of growth inhibition in transformed cells supporting a connection between these gene family members and metastasis. [provided by RefSeq, May 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13305098).
BS2
High AC in GnomAdExome4 at 35 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTA2NM_004739.4 linkc.1939C>T p.Pro647Ser missense_variant Exon 18 of 18 ENST00000278823.7 NP_004730.2 O94776-1A0A024R534
MTA2NM_001330292.2 linkc.1420C>T p.Pro474Ser missense_variant Exon 18 of 18 NP_001317221.1 O94776-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTA2ENST00000278823.7 linkc.1939C>T p.Pro647Ser missense_variant Exon 18 of 18 1 NM_004739.4 ENSP00000278823.2 O94776-1
MTA2ENST00000524902.5 linkc.1420C>T p.Pro474Ser missense_variant Exon 16 of 16 1 ENSP00000431346.1 O94776-2
MTA2ENST00000527204.5 linkc.1420C>T p.Pro474Ser missense_variant Exon 18 of 18 2 ENSP00000431797.1 O94776-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152216
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
250984
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135648
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.00
Gnomad NFE exome
AF:
0.0000441
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000239
AC:
35
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.0000303
AC XY:
22
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152216
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T;.;.
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.090
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.80
T;.;T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;.;.
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-2.2
N;D;D
REVEL
Benign
0.041
Sift
Uncertain
0.020
D;D;D
Sift4G
Benign
0.066
T;T;T
Polyphen
0.084
B;.;.
Vest4
0.31
MutPred
0.30
Loss of catalytic residue at P647 (P = 0.0172);.;.;
MVP
0.29
MPC
0.49
ClinPred
0.13
T
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.13
gMVP
0.29

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

LitVar

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

Other links and lift over

dbSNP: rs778548131; hg19: chr11-62361415; API