2-42644172-C-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001330442.2(MTA3):​c.427C>G​(p.Leu143Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

MTA3
NM_001330442.2 missense

Scores

4
12
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66
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 -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.785
BS2
High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTA3NM_001330442.2 linkc.427C>G p.Leu143Val missense_variant Exon 6 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.427C>G p.Leu143Val missense_variant Exon 6 of 17 5 NM_001330442.2 ENSP00000385823.1 Q9BTC8-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1460794
Hom.:
0
Cov.:
29
AF XY:
0.00000688
AC XY:
5
AN XY:
726672
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000900
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.427C>G (p.L143V) alteration is located in exon 6 (coding exon 6) of the MTA3 gene. This alteration results from a C to G substitution at nucleotide position 427, causing the leucine (L) at amino acid position 143 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
0.73
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.73
D;D;.;D;D
Eigen
Benign
0.042
Eigen_PC
Benign
-0.082
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.98
.;D;D;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.78
D;D;D;D;D
MetaSVM
Uncertain
0.44
D
MutationAssessor
Pathogenic
3.2
.;.;M;.;M
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-2.7
D;D;D;D;D
REVEL
Uncertain
0.62
Sift
Uncertain
0.026
D;D;D;D;D
Sift4G
Uncertain
0.0090
D;D;D;D;D
Polyphen
0.99
D;D;P;P;.
Vest4
0.83
MutPred
0.45
Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);.;.;.;
MVP
0.89
MPC
0.67
ClinPred
0.94
D
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.54

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: rs368239450; hg19: chr2-42871312; API