14-105465168-G-C

Position:

• chr14-105465168-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004689.4(MTA1):​c.1609G>C​(p.Val537Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: MTA1 NM_004689.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42107123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTA1	NM_004689.4	c.1609G>C	p.Val537Leu	missense_variant	16/21	ENST00000331320.12	NP_004680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTA1	ENST00000331320.12	c.1609G>C	p.Val537Leu	missense_variant	16/21	1	NM_004689.4	ENSP00000333633.7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2023

The c.1609G>C (p.V537L) alteration is located in exon 16 (coding exon 16) of the MTA1 gene. This alteration results from a G to C substitution at nucleotide position 1609, causing the valine (V) at amino acid position 537 to be replaced by a leucine (L). 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	0.67
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T;T;T;.;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.42	T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.7	.;L;.;.;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.029	D;D;D;D;D
Sift4G	Benign	0.27	T;T;T;T;T
Polyphen		0.91	.;P;.;.;.
Vest4		0.64
MutPred		0.32		.;Loss of methylation at K532 (P = 0.0857);Loss of methylation at K532 (P = 0.0857);.;.;
MVP		0.42
MPC		1.3
ClinPred		0.85	D
GERP RS		5.4
Varity_R		0.66
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-105931505;