X-101884418-G-T

Variant names:

• chrX-101884418-G-T
• rs201873364
• NM_001394560.1:c.1180C>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001394560.1(ZMAT1):​c.1180C>A​(p.His394Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,097,753 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000010 (0 hom. 3 hem.)
• Consequence: ZMAT1 NM_001394560.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.02

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.070703804).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMAT1	NM_001394560.1	c.1180C>A	p.His394Asn	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.1180C>A	p.His394Asn	missense_variant	Exon 6 of 6		NM_001394560.1	ENSP00000498446.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000100 AC: 11 AN: 1097753 Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 3 AN XY: 363357

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000131

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Alfa AF: 0.0000660 Hom.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1009C>A (p.H337N) alteration is located in exon 7 (coding exon 6) of the ZMAT1 gene. This alteration results from a C to A substitution at nucleotide position 1009, causing the histidine (H) at amino acid position 337 to be replaced by an asparagine (N). 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	0.10
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.41
DANN	Benign	0.42
FATHMM_MKL	Benign	0.040	N
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.0070
Sift	Benign	0.32	T;T
Sift4G	Benign	0.14	T;T
Vest4		0.093
MutPred		0.19		Loss of catalytic residue at H337 (P = 0.0482);Loss of catalytic residue at H337 (P = 0.0482);
MVP		0.21
MPC		0.10
ClinPred		0.12	T
GERP RS		-0.62
gMVP		0.089

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: rs201873364; hg19: chrX-101139390;