X-101884261-T-G

Variant names:

• chrX-101884261-T-G
• rs372963755
• NM_001394560.1:c.1337A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001394560.1(ZMAT1):​c.1337A>C​(p.Tyr446Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,209,104 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000047 (0 hom. 11 hem.)
• Consequence: ZMAT1 NM_001394560.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.591
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07665235).
• BS2: High Hemizygotes in GnomAdExome4 at 11 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.1337A>C	p.Tyr446Ser	missense	Exon 6 of 6	NP_001381489.1	Q5H9K5-3
	ZMAT1	NM_001011657.4		c.1166A>C	p.Tyr389Ser	missense	Exon 7 of 7	NP_001011657.2	Q5H9K5-1
	ZMAT1	NM_001282400.2		c.653A>C	p.Tyr218Ser	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.1337A>C	p.Tyr446Ser	missense	Exon 6 of 6	ENSP00000498446.1	Q5H9K5-3
	ZMAT1	ENST00000372782.4	TSL:1	c.1166A>C	p.Tyr389Ser	missense	Exon 7 of 7	ENSP00000361868.3	Q5H9K5-1
	ZMAT1	ENST00000878190.1		c.1406A>C	p.Tyr469Ser	missense	Exon 7 of 7	ENSP00000548249.1

Frequencies

GnomAD3 genomes AF: 0.0000449 AC: 5 AN: 111362 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000758

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000566

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000711 AC: 13 AN: 182881 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000732

Gnomad ASJ exome AF: 0.00107

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000474 AC: 52 AN: 1097742 Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 11 AN XY: 363336

African (AFR) AF: 0.00 AC: 0 AN: 26369

American (AMR) AF: 0.0000569 AC: 2 AN: 35151

Ashkenazi Jewish (ASJ) AF: 0.00108 AC: 21 AN: 19359

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54113

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.0000297 AC: 25 AN: 841841

Other (OTH) AF: 0.0000868 AC: 4 AN: 46072

GnomAD4 genome AF: 0.0000449 AC: 5 AN: 111362 Hom.: 0 Cov.: 22 AF XY: 0.0000297 AC XY: 1 AN XY: 33664

African (AFR) AF: 0.00 AC: 0 AN: 30581

American (AMR) AF: 0.00 AC: 0 AN: 10474

Ashkenazi Jewish (ASJ) AF: 0.000758 AC: 2 AN: 2639

East Asian (EAS) AF: 0.00 AC: 0 AN: 3484

South Asian (SAS) AF: 0.00 AC: 0 AN: 2662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6120

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

European-Non Finnish (NFE) AF: 0.0000566 AC: 3 AN: 52987

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

Alfa AF: 0.000130 Hom.: 1

Bravo AF: 0.0000491

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000659 AC: 8

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	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.83
FATHMM_MKL	Uncertain	0.76	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.59
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.070
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.011	D
Vest4		0.17
MVP		0.17
MPC		0.14
ClinPred		0.31	T
GERP RS		2.1
gMVP		0.19
Mutation Taster		=94/6	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: rs372963755; hg19: chrX-101139233;