X-101884481-T-C

Variant names:

• chrX-101884481-T-C
• NM_001394560.1:c.1117A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394560.1(ZMAT1):​c.1117A>G​(p.Lys373Glu) 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: 23)
• Consequence: ZMAT1 NM_001394560.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.43

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21733764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMAT1	NM_001394560.1	c.1117A>G	p.Lys373Glu	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.1117A>G	p.Lys373Glu	missense_variant	Exon 6 of 6		NM_001394560.1	ENSP00000498446.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.946A>G (p.K316E) alteration is located in exon 7 (coding exon 6) of the ZMAT1 gene. This alteration results from a A to G substitution at nucleotide position 946, causing the lysine (K) at amino acid position 316 to be replaced by a glutamic acid (E). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0080	D;D
Vest4		0.16
MutPred		0.47		Loss of methylation at K316 (P = 0.0025);Loss of methylation at K316 (P = 0.0025);
MVP		0.49
MPC		0.51
ClinPred		0.93	D
GERP RS		4.3
gMVP		0.40

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: chrX-101139453;