Variant 17-15981113-CAT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_001042697.2(ZSWIM7):c.231_232delAT(p.Cys78fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

ZSWIM7
NM_001042697.2 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 7.72

Variant links:

Genes affected

ZSWIM7 (HGNC:26993): (zinc finger SWIM-type containing 7) Predicted to enable zinc ion binding activity. Involved in double-strand break repair via homologous recombination and protein stabilization. Part of Shu complex. [provided by Alliance of Genome Resources, Apr 2022]

ZSWIM7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.454 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-15981113-CAT-C is Pathogenic according to our data. Variant chr17-15981113-CAT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1013608.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSWIM7	NM_001042697.2 link	c.231_232delAT	p.Cys78fs	frameshift_variant	4/5	ENST00000399277.6	NP_001036162.1	Q19AV6A0A024RD64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSWIM7	ENST00000399277.6 link	c.231_232delAT	p.Cys78fs	frameshift_variant	4/5	1	NM_001042697.2	ENSP00000382218.1		Q19AV6

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000365

AC:

AN:

249446

Hom.:

AF XY:

0.000384

AC XY:

AN XY:

135326

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.000389

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000406

Gnomad OTH exome

AF:

0.000495

GnomAD4 exome

AF:

0.000340

AC:

497

AN:

1461524

Hom.:

AF XY:

0.000330

AC XY:

240

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000454

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000352

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000420

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000861

Hom.:

Bravo

AF:

0.000351

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000593

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ovarian dysgenesis 10

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Jul 07, 2022

ACMG classification criteria: PVS1 very strong, PM3 moderated -

Spermatogenic failure 71

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 08, 2022

- -

Non-obstructive azoospermia

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Molecular and Cell Genetics Laboratory, University of Science and Technology of China

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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