X-101883913-T-G

Variant names:

• chrX-101883913-T-G
• rs1412431932
• NM_001394560.1:c.1685A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394560.1(ZMAT1):​c.1685A>C​(p.Glu562Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,230 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: ZMAT1 NM_001394560.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19028741).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394560.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT1	NM_001394560.1	MANE Select	c.1685A>C	p.Glu562Ala	missense	Exon 6 of 6	NP_001381489.1	Q5H9K5-3
	ZMAT1	NM_001011657.4		c.1514A>C	p.Glu505Ala	missense	Exon 7 of 7	NP_001011657.2	Q5H9K5-1
	ZMAT1	NM_001282400.2		c.1001A>C	p.Glu334Ala	missense	Exon 10 of 10	NP_001269329.1	Q5H9K5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT1	ENST00000651725.2	MANE Select	c.1685A>C	p.Glu562Ala	missense	Exon 6 of 6	ENSP00000498446.1	Q5H9K5-3
	ZMAT1	ENST00000372782.4	TSL:1	c.1514A>C	p.Glu505Ala	missense	Exon 7 of 7	ENSP00000361868.3	Q5H9K5-1
	ZMAT1	ENST00000878190.1		c.1754A>C	p.Glu585Ala	missense	Exon 7 of 7	ENSP00000548249.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097230 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 1 AN XY: 362966

African (AFR) AF: 0.0000380 AC: 1 AN: 26343

American (AMR) AF: 0.00 AC: 0 AN: 35038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19322

East Asian (EAS) AF: 0.00 AC: 0 AN: 30181

South Asian (SAS) AF: 0.00 AC: 0 AN: 54071

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841695

Other (OTH) AF: 0.0000217 AC: 1 AN: 46033

GnomAD4 genome Cov.: 22

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	0.99
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.5
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.093
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Vest4		0.051
MutPred		0.19		Loss of solvent accessibility (P = 0.0224)
MVP		0.37
MPC		0.36
ClinPred		0.95	D
GERP RS		4.4
gMVP		0.27
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1412431932; hg19: chrX-101138885;