X-101883608-C-T

Variant names:

• chrX-101883608-C-T
• rs749373831
• NM_001394560.1:c.1990G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001394560.1(ZMAT1):​c.1990G>A​(p.Glu664Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000315 in 1,205,757 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000091 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000034 (0 hom. 16 hem.)
• Consequence: ZMAT1 NM_001394560.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05647418).
• BS2: High Hemizygotes in GnomAdExome4 at 16 gene

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.1990G>A	p.Glu664Lys	missense	Exon 6 of 6	NP_001381489.1	Q5H9K5-3
	ZMAT1	NM_001011657.4		c.1819G>A	p.Glu607Lys	missense	Exon 7 of 7	NP_001011657.2	Q5H9K5-1
	ZMAT1	NM_001282400.2		c.1306G>A	p.Glu436Lys	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.1990G>A	p.Glu664Lys	missense	Exon 6 of 6	ENSP00000498446.1	Q5H9K5-3
	ZMAT1	ENST00000372782.4	TSL:1	c.1819G>A	p.Glu607Lys	missense	Exon 7 of 7	ENSP00000361868.3	Q5H9K5-1
	ZMAT1	ENST00000878190.1		c.2059G>A	p.Glu687Lys	missense	Exon 7 of 7	ENSP00000548249.1

Frequencies

GnomAD3 genomes AF: 0.00000914 AC: 1 AN: 109358 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000980

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000605 AC: 11 AN: 181737 AF XY: 0.0000450

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000368

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000337 AC: 37 AN: 1096399 Hom.: 0 Cov.: 32 AF XY: 0.0000441 AC XY: 16 AN XY: 362409

African (AFR) AF: 0.00 AC: 0 AN: 26301

American (AMR) AF: 0.000285 AC: 10 AN: 35027

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19338

East Asian (EAS) AF: 0.00 AC: 0 AN: 30189

South Asian (SAS) AF: 0.00 AC: 0 AN: 53986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.0000297 AC: 25 AN: 841669

Other (OTH) AF: 0.0000435 AC: 2 AN: 46026

GnomAD4 genome AF: 0.00000914 AC: 1 AN: 109358 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 31802

African (AFR) AF: 0.00 AC: 0 AN: 30081

American (AMR) AF: 0.0000980 AC: 1 AN: 10200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2620

East Asian (EAS) AF: 0.00 AC: 0 AN: 3479

South Asian (SAS) AF: 0.00 AC: 0 AN: 2457

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52389

Other (OTH) AF: 0.00 AC: 0 AN: 1497

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000412 AC: 5

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	0.093
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.67
FATHMM_MKL	Benign	0.21	N
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.057
Sift	Benign	0.45	T
Sift4G	Benign	0.51	T
Vest4		0.13
MutPred		0.13		Gain of methylation at E607 (P = 0.0159)
MVP		0.15
MPC		0.15
ClinPred		0.060	T
GERP RS		2.3
gMVP		0.15
Mutation Taster		=95/5	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: rs749373831; hg19: chrX-101138580; COSMIC: COSV100858822; COSMIC: COSV100858822;