rs193920814

Variant names:

• chr3-179067571-C-T
• rs193920814
• NM_022470.4:c.182G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022470.4(ZMAT3):​c.182G>A​(p.Cys61Tyr) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C61S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZMAT3 NM_022470.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.28
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046714127).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022470.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT3	NM_022470.4	MANE Select	c.182G>A	p.Cys61Tyr	missense	Exon 2 of 6	NP_071915.1
	ZMAT3	NM_001375824.1		c.182G>A	p.Cys61Tyr	missense	Exon 2 of 6	NP_001362753.1
	ZMAT3	NM_001375825.1		c.182G>A	p.Cys61Tyr	missense	Exon 2 of 6	NP_001362754.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT3	ENST00000311417.7	TSL:1 MANE Select	c.182G>A	p.Cys61Tyr	missense	Exon 2 of 6	ENSP00000311221.2
	ZMAT3	ENST00000652290.1		c.182G>A	p.Cys61Tyr	missense	Exon 2 of 10	ENSP00000498847.1
	ZMAT3	ENST00000432729.5	TSL:2	c.182G>A	p.Cys61Tyr	missense	Exon 3 of 7	ENSP00000396506.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.31
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.3
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.11
Sift	Benign	0.86	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.35		Loss of helix (P = 0.0033)
MVP		0.35
MPC		0.40
ClinPred		0.10	T
GERP RS		3.8
Varity_R		0.11
gMVP		0.19
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs193920814; hg19: chr3-178785359; COSMIC: COSV60995681;