rs370573471

Variant names:

• chr11-62598035-C-T
• rs370573471
• NM_004739.4:c.479G>A

Variant summary

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

The NM_004739.4(MTA2):​c.479G>A​(p.Arg160His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MTA2 NM_004739.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04

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]

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=0.16791734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTA2	NM_004739.4	c.479G>A	p.Arg160His	missense_variant	Exon 6 of 18	ENST00000278823.7	NP_004730.2
MTA2	NM_001330292.2	c.-41G>A		5_prime_UTR_variant	Exon 6 of 18		NP_001317221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTA2	ENST00000278823.7	c.479G>A	p.Arg160His	missense_variant	Exon 6 of 18	1	NM_004739.4	ENSP00000278823.2
MTA2	ENST00000524902.5	c.-41G>A		5_prime_UTR_variant	Exon 4 of 16	1		ENSP00000431346.1
MTA2	ENST00000527204.5	c.-41G>A		5_prime_UTR_variant	Exon 6 of 18	2		ENSP00000431797.1
MTA2	ENST00000531261.1	n.95G>A		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461658 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727154

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.479G>A (p.R160H) alteration is located in exon 6 (coding exon 6) of the MTA2 gene. This alteration results from a G to A substitution at nucleotide position 479, causing the arginine (R) at amino acid position 160 to be replaced by a histidine (H). 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	0.086
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.024
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.70	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.11
Sift	Benign	0.45	T
Sift4G	Benign	0.35	T
Polyphen		0.89	P
Vest4		0.24
MVP		0.49
MPC		0.86
ClinPred		0.68	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.069
gMVP		0.31

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

Other links and lift over

dbSNP: rs370573471; hg19: chr11-62365507; COSMIC: COSV53871317; COSMIC: COSV53871317;