Genetic Variant ZMAT1:p.Pro662Ser (chrX-101883614-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001394560.1(ZMAT1):c.1984C>T(p.Pro662Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,204,313 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., 26 hem., cov: 21)

Exomes 𝑓: 0.000064 ( 0 hom. 16 hem. )

Consequence

ZMAT1
NM_001394560.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.765

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007716149).

BP6

Variant X-101883614-G-A is Benign according to our data. Variant chrX-101883614-G-A is described in ClinVar as Benign. ClinVar VariationId is 208893.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 26 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.1984C>T	p.Pro662Ser	missense	Exon 6 of 6	NP_001381489.1	Q5H9K5-3
ZMAT1	NM_001011657.4		c.1813C>T	p.Pro605Ser	missense	Exon 7 of 7	NP_001011657.2	Q5H9K5-1
ZMAT1	NM_001282400.2		c.1300C>T	p.Pro434Ser	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.1984C>T	p.Pro662Ser	missense	Exon 6 of 6	ENSP00000498446.1	Q5H9K5-3
ZMAT1	ENST00000372782.4	TSL:1	c.1813C>T	p.Pro605Ser	missense	Exon 7 of 7	ENSP00000361868.3	Q5H9K5-1
ZMAT1	ENST00000878190.1		c.2053C>T	p.Pro685Ser	missense	Exon 7 of 7	ENSP00000548249.1

Frequencies

GnomAD3 genomes

AF:

0.000724

AC:

AN:

107757

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000994

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:

0.000225

AC:

AN:

182039

AF XY:

0.0000897

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.000257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.0000638

AC:

AN:

1096506

Hom.:

Cov.:

AF XY:

0.0000441

AC XY:

AN XY:

362418

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

26334

American (AMR)

AF:

0.000314

AC:

AN:

35073

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19351

East Asian (EAS)

AF:

0.00

AC:

AN:

30189

South Asian (SAS)

AF:

0.00

AC:

AN:

54016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

841634

Other (OTH)

AF:

0.000152

AC:

AN:

46035

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.000714

AC:

AN:

107807

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

30743

show subpopulations

African (AFR)

AF:

0.00256

AC:

AN:

29658

American (AMR)

AF:

0.0000992

AC:

AN:

10076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2584

East Asian (EAS)

AF:

0.00

AC:

AN:

3434

South Asian (SAS)

AF:

0.00

AC:

AN:

2356

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5515

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51800

Other (OTH)

AF:

0.00

AC:

AN:

1486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000208

Hom.:

Bravo

AF:

0.000899

ESP6500AA

AF:

0.00391

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000231

AC:

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Abnormality of neuronal migration (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.94

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.061

(source)

DANN

Benign

0.18

FATHMM_MKL

Benign

0.019

M_CAP

Benign

0.025

MetaRNN

Benign

0.0077

MetaSVM

Benign

-0.97

PhyloP100

-0.77

PrimateAI

Benign

0.24

PROVEAN

Benign

0.27

REVEL

Benign

0.034

Sift

Benign

0.66

Sift4G

Benign

1.0

Vest4

0.047

MVP

0.040

MPC

0.091

ClinPred

0.0068

GERP RS

-0.34

gMVP

0.047

Mutation Taster

=98/2

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