Variant chr22-29731314-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001003692.2(ZMAT5):c.424G>T(p.Gly142Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000261 in 1,531,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

ZMAT5
NM_001003692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58

Variant links:

Genes affected

ZMAT5 (HGNC:28046): (zinc finger matrin-type 5) Predicted to enable zinc ion binding activity. Predicted to be involved in RNA splicing. Located in nucleoplasm. Part of U12-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ZMAT5 links:

CABP7 (HGNC:20834): (calcium binding protein 7) Predicted to enable calcium ion binding activity. Located in trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

CABP7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZMAT5	NM_001003692.2 linkuse as main transcript	c.424G>T	p.Gly142Cys	missense_variant	6/6	ENST00000344318.4	NP_001003692.1
CABP7	NM_182527.3 linkuse as main transcript	c.*1745C>A		3_prime_UTR_variant	5/5	ENST00000216144.4	NP_872333.1
ZMAT5	NM_001318129.2 linkuse as main transcript	c.424G>T	p.Gly142Cys	missense_variant	6/6		NP_001305058.1
ZMAT5	NM_019103.3 linkuse as main transcript	c.424G>T	p.Gly142Cys	missense_variant	7/7		NP_061976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMAT5	ENST00000344318.4 linkuse as main transcript	c.424G>T	p.Gly142Cys	missense_variant	6/6	1	NM_001003692.2	ENSP00000344241	P1
CABP7	ENST00000216144.4 linkuse as main transcript	c.*1745C>A		3_prime_UTR_variant	5/5	1	NM_182527.3	ENSP00000216144	P1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152082

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000564

AC:

AN:

177194

Hom.:

AF XY:

0.0000102

AC XY:

AN XY:

98246

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1379324

Hom.:

Cov.:

AF XY:

0.00000292

AC XY:

AN XY:

684362

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000277

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000870

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.424G>T (p.G142C) alteration is located in exon 7 (coding exon 5) of the ZMAT5 gene. This alteration results from a G to T substitution at nucleotide position 424, causing the glycine (G) at amino acid position 142 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.78

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.54

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.22

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.021

Polyphen

0.94

Vest4

0.75

MutPred

0.39

Gain of catalytic residue at G142 (P = 0.0496);

MVP

0.15

ClinPred

0.89

GERP RS

5.3

Varity_R

0.28

gMVP

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over