dbSNP rs746916762: ZMAT1:p.Asp628Val (chrX-101883715-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001394560.1(ZMAT1):c.1883A>T(p.Asp628Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,205,640 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 134 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.00021 ( 0 hom. 130 hem. )

Consequence

ZMAT1
NM_001394560.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010410011).

BP6

Variant X-101883715-T-A is Benign according to our data. Variant chrX-101883715-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2661073.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 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.1883A>T	p.Asp628Val	missense	Exon 6 of 6	NP_001381489.1	Q5H9K5-3
ZMAT1	NM_001011657.4		c.1712A>T	p.Asp571Val	missense	Exon 7 of 7	NP_001011657.2	Q5H9K5-1
ZMAT1	NM_001282400.2		c.1199A>T	p.Asp400Val	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.1883A>T	p.Asp628Val	missense	Exon 6 of 6	ENSP00000498446.1	Q5H9K5-3
ZMAT1	ENST00000372782.4	TSL:1	c.1712A>T	p.Asp571Val	missense	Exon 7 of 7	ENSP00000361868.3	Q5H9K5-1
ZMAT1	ENST00000878190.1		c.1952A>T	p.Asp651Val	missense	Exon 7 of 7	ENSP00000548249.1

Frequencies

GnomAD3 genomes

AF:

0.0000633

AC:

AN:

110609

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000657

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00118

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000379

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000279

AC:

AN:

179319

AF XY:

0.000446

show subpopulations

Gnomad AFR exome

AF:

0.000230

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000139

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000621

Gnomad OTH exome

AF:

0.000455

GnomAD4 exome

AF:

0.000211

AC:

231

AN:

1094979

Hom.:

Cov.:

AF XY:

0.000360

AC XY:

130

AN XY:

361585

show subpopulations

African (AFR)

AF:

0.0000770

AC:

AN:

25973

American (AMR)

AF:

0.00

AC:

AN:

34467

Ashkenazi Jewish (ASJ)

AF:

0.0000520

AC:

AN:

19218

East Asian (EAS)

AF:

0.00

AC:

AN:

30186

South Asian (SAS)

AF:

0.00282

AC:

151

AN:

53572

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40265

Middle Eastern (MID)

AF:

0.00268

AC:

AN:

4099

European-Non Finnish (NFE)

AF:

0.0000654

AC:

AN:

841301

Other (OTH)

AF:

0.000240

AC:

AN:

45898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000633

AC:

AN:

110661

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

32943

show subpopulations

African (AFR)

AF:

0.0000655

AC:

AN:

30525

American (AMR)

AF:

0.00

AC:

AN:

10360

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2620

East Asian (EAS)

AF:

0.00

AC:

AN:

3498

South Asian (SAS)

AF:

0.00119

AC:

AN:

2531

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5961

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000379

AC:

AN:

52749

Other (OTH)

AF:

0.00

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000338

AC:

EpiCase

AF:

0.000219

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.94

FATHMM_MKL

Benign

0.33

M_CAP

Benign

0.0048

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.99

PhyloP100

1.1

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.092

Sift

Uncertain

0.0020

Sift4G

Benign

0.34

Vest4

0.17

MutPred

0.26

Loss of ubiquitination at K572 (P = 0.0227)

MVP

0.17

MPC

0.28

ClinPred

0.057

GERP RS

-3.2

gMVP

0.24

Mutation Taster

=99/1

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over