Genetic Variant ZMAT1:p.Glu520Gly (chrX-101884039-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001394560.1(ZMAT1):c.1559A>G(p.Glu520Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,096,909 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. 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: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 3 hem. )

Consequence

ZMAT1
NM_001394560.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Publications

0 publications found

Variant links:

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]

ZMAT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2259734).

BS2

High Hemizygotes in GnomAdExome4 at 3 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMAT1	NM_001394560.1	MANE Select	c.1559A>G	p.Glu520Gly	missense	Exon 6 of 6	NP_001381489.1	Q5H9K5-3
ZMAT1	NM_001011657.4		c.1388A>G	p.Glu463Gly	missense	Exon 7 of 7	NP_001011657.2	Q5H9K5-1
ZMAT1	NM_001282400.2		c.875A>G	p.Glu292Gly	missense	Exon 10 of 10	NP_001269329.1	Q5H9K5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMAT1	ENST00000651725.2	MANE Select	c.1559A>G	p.Glu520Gly	missense	Exon 6 of 6	ENSP00000498446.1	Q5H9K5-3
ZMAT1	ENST00000372782.4	TSL:1	c.1388A>G	p.Glu463Gly	missense	Exon 7 of 7	ENSP00000361868.3	Q5H9K5-1
ZMAT1	ENST00000878190.1		c.1628A>G	p.Glu543Gly	missense	Exon 7 of 7	ENSP00000548249.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1096909

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

362813

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26363

American (AMR)

AF:

0.00

AC:

AN:

35107

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19362

East Asian (EAS)

AF:

0.00

AC:

AN:

30195

South Asian (SAS)

AF:

0.00

AC:

AN:

54125

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39675

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4133

European-Non Finnish (NFE)

AF:

0.00000356

AC:

AN:

841894

Other (OTH)

AF:

0.00

AC:

AN:

46055

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

FATHMM_MKL

Benign

0.58

M_CAP

Benign

0.0088

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.92

PhyloP100

1.6

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.11

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Vest4

0.055

MutPred

0.51

Loss of loop (P = 0.0128)

MVP

0.37

MPC

0.44

ClinPred

0.99

GERP RS

4.4

gMVP

0.34

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over