Genetic Variant NM_001394560.1:c.1488G>A (chrX-101884110-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394560.1(ZMAT1):c.1488G>A(p.Met496Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,207,848 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

ZMAT1
NM_001394560.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.250

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08139947).

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.1488G>A	p.Met496Ile	missense	Exon 6 of 6	NP_001381489.1	Q5H9K5-3
ZMAT1	NM_001011657.4		c.1317G>A	p.Met439Ile	missense	Exon 7 of 7	NP_001011657.2	Q5H9K5-1
ZMAT1	NM_001282400.2		c.804G>A	p.Met268Ile	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.1488G>A	p.Met496Ile	missense	Exon 6 of 6	ENSP00000498446.1	Q5H9K5-3
ZMAT1	ENST00000372782.4	TSL:1	c.1317G>A	p.Met439Ile	missense	Exon 7 of 7	ENSP00000361868.3	Q5H9K5-1
ZMAT1	ENST00000878190.1		c.1557G>A	p.Met519Ile	missense	Exon 7 of 7	ENSP00000548249.1

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112167

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000553

AC:

AN:

180717

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

9.13e-7

AC:

AN:

1095681

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362017

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26366

American (AMR)

AF:

0.00

AC:

AN:

35133

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19345

East Asian (EAS)

AF:

0.00

AC:

AN:

30189

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54093

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38743

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841653

Other (OTH)

AF:

0.00

AC:

AN:

46031

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00000892

AC:

AN:

112167

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34387

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30914

American (AMR)

AF:

0.00

AC:

AN:

10603

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3541

South Asian (SAS)

AF:

0.00

AC:

AN:

2716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6139

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53156

Other (OTH)

AF:

0.00

AC:

AN:

1525

Age Distribution

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

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.5

(source)

DANN

Benign

0.69

FATHMM_MKL

Benign

0.027

M_CAP

Benign

0.053

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.1

PhyloP100

0.25

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.2

REVEL

Benign

0.011

Sift

Benign

0.10

Sift4G

Benign

0.14

Vest4

0.10

MutPred

0.33

Loss of catalytic residue at M439 (P = 0.0418)

MVP

0.26

MPC

0.10

ClinPred

0.067

GERP RS

-0.41

gMVP

0.10

Mutation Taster

=95/5

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

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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