Genetic Variant ZMAT5:p.Val141Leu (chr22-29731317-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001003692.2(ZMAT5):c.421G>C(p.Val141Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000392 in 1,531,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

ZMAT5
NM_001003692.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.373

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017976493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMAT5	NM_001003692.2 link	c.421G>C	p.Val141Leu	missense_variant	Exon 6 of 6	ENST00000344318.4	NP_001003692.1	Q9UDW3A0A024R1I1
CABP7	NM_182527.3 link	c.*1748C>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000216144.4	NP_872333.1	Q86V35
ZMAT5	NM_001318129.2 link	c.421G>C	p.Val141Leu	missense_variant	Exon 6 of 6		NP_001305058.1	Q9UDW3A0A024R1I1
ZMAT5	NM_019103.3 link	c.421G>C	p.Val141Leu	missense_variant	Exon 7 of 7		NP_061976.1	Q9UDW3A0A024R1I1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMAT5	ENST00000344318.4 link	c.421G>C	p.Val141Leu	missense_variant	Exon 6 of 6	1	NM_001003692.2	ENSP00000344241.3		Q9UDW3
CABP7	ENST00000216144.4 link	c.*1748C>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_182527.3	ENSP00000216144.3		Q86V35

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152066

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:

177198

Hom.:

AF XY:

0.00

AC XY:

AN XY:

98234

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:

0.00000363

AC:

AN:

1379294

Hom.:

Cov.:

AF XY:

0.00000292

AC XY:

AN XY:

684274

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:

0.00000462

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74272

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:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.52

DANN

Benign

0.65

DEOGEN2

Benign

0.0068

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.59

M_CAP

Benign

0.0076

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.20

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.020

REVEL

Benign

0.0080

Sift

Benign

0.90

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.033

MutPred

0.18

Gain of catalytic residue at V141 (P = 0.074);

MVP

0.014

ClinPred

0.0087

GERP RS

-7.4

Varity_R

0.029

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over