chr2-42656271-C-G

Variant summary

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

The NM_001330442.2(MTA3):​c.571C>G​(p.Arg191Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,358 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

MTA3
NM_001330442.2 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27
Variant links:
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]

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=0.15821117).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTA3NM_001330442.2 linkc.571C>G p.Arg191Gly missense_variant Exon 7 of 17 ENST00000405094.2 NP_001317371.1 Q9BTC8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTA3ENST00000405094.2 linkc.571C>G p.Arg191Gly missense_variant Exon 7 of 17 5 NM_001330442.2 ENSP00000385823.1 Q9BTC8-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000682
AC:
17
AN:
249116
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135152
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00139
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1461274
Hom.:
0
Cov.:
30
AF XY:
0.0000234
AC XY:
17
AN XY:
726936
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00103
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152084
Hom.:
0
Cov.:
32
AF XY:
0.0000539
AC XY:
4
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000900
Hom.:
0
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000244
AC:
2
ExAC
AF:
0.0000331
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.571C>G (p.R191G) alteration is located in exon 7 (coding exon 7) of the MTA3 gene. This alteration results from a C to G substitution at nucleotide position 571, causing the arginine (R) at amino acid position 191 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
0.33
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.040
T;T;.;T;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.96
.;D;D;D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.16
T;T;T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Uncertain
2.5
.;.;M;.;M
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-5.1
D;D;D;D;D
REVEL
Benign
0.12
Sift
Uncertain
0.0050
D;D;D;D;D
Sift4G
Uncertain
0.024
D;D;D;D;D
Polyphen
0.94
P;P;P;B;.
Vest4
0.50
MVP
0.32
MPC
0.25
ClinPred
0.81
D
GERP RS
5.1
Varity_R
0.52
gMVP
0.46

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

LitVar

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

Other links and lift over

dbSNP: rs368905145; hg19: chr2-42883411; API