chr3-179027464-A-T

Position:

• chr3-179027464-A-T

Variant summary

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

The NM_022470.4(ZMAT3):​c.617T>A​(p.Met206Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZMAT3 NM_022470.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.04

Genes affected

ZMAT3 (HGNC:29983): (zinc finger matrin-type 3) This gene encodes a protein containing three zinc finger domains and a nuclear localization signal. The mRNA and the protein of this gene are upregulated by wildtype p53 and overexpression of this gene inhibits tumor cell growth, suggesting that this gene may have a role in the p53-dependent growth regulatory pathway. Alternative splicing of this gene results in two transcript variants encoding two isoforms differing in only one amino acid. [provided by RefSeq, Jul 2008]

ZMAT3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMAT3	NM_022470.4	c.617T>A	p.Met206Lys	missense_variant	5/6	ENST00000311417.7	NP_071915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMAT3	ENST00000311417.7	c.617T>A	p.Met206Lys	missense_variant	5/6	1	NM_022470.4	ENSP00000311221.2
ZMAT3	ENST00000652290.1	c.617T>A	p.Met206Lys	missense_variant	5/10			ENSP00000498847.1
ZMAT3	ENST00000432729.5	c.617T>A	p.Met206Lys	missense_variant	6/7	2		ENSP00000396506.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Aug 23, 2021

The c.617T>A (p.M206K) alteration is located in exon 5 (coding exon 4) of the ZMAT3 gene. This alteration results from a T to A substitution at nucleotide position 617, causing the methionine (M) at amino acid position 206 to be replaced by a lysine (K). 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	0.27
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.058	T;.
Eigen	Benign	-0.073
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.69	N;N
REVEL	Benign	0.14
Sift	Benign	0.13	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.15	B;B
Vest4		0.71
MutPred		0.33		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.67
MPC		0.39
ClinPred		0.68	D
GERP RS		5.6
Varity_R		0.40
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-178745252;