X-101883775-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_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

Scores

14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.406
Variant links:
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]

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ACMG classification

Classification made for transcript

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
ZMAT1NM_001394560.1 linkc.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
ZMAT1ENST00000651725.2 linkc.1823G>A p.Arg608Lys missense_variant Exon 6 of 6 NM_001394560.1 ENSP00000498446.1 A0A494C0A7

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
LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs867057521; hg19: chrX-101138747; API