X-101883775-C-T

Variant names:

• chrX-101883775-C-T
• rs867057521
• NM_001394560.1:c.1823G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001394560.1(ZMAT1):​c.1823G>A​(p.Arg608Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ZMAT1 NM_001394560.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.406

Genes affected

ZMAT1 (HGNC:29377): (zinc finger matrin-type 1) This gene encodes a protein containing Cys2-His2 (C2H2)-type zinc fingers, which are similar to those found in the nuclear matrix protein matrin 3. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037518412).
• BP6: Variant X-101883775-C-T is Benign according to our data. Variant chrX-101883775-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3473955.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMAT1	NM_001394560.1	c.1823G>A	p.Arg608Lys	missense_variant	Exon 6 of 6	ENST00000651725.2	NP_001381489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMAT1	ENST00000651725.2	c.1823G>A	p.Arg608Lys	missense_variant	Exon 6 of 6		NM_001394560.1	ENSP00000498446.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 13, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.85
FATHMM_MKL	Benign	0.057	N
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.034
Sift	Benign	0.73	T;T
Sift4G	Benign	0.42	T;T
Vest4		0.051
MutPred		0.23		Gain of methylation at R551 (P = 0.0043);Gain of methylation at R551 (P = 0.0043);
MVP		0.20
MPC		0.093
ClinPred		0.052	T
GERP RS		-0.055
gMVP		0.11

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: rs867057521; hg19: chrX-101138747;