rs1045599

Variant names:

• chr17-15976596-C-T
• rs1045599
• ENST00000490395.5:n.*1076G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000490395.5(ZSWIM7):​n.*1076G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,934 control chromosomes in the GnomAD database, including 27,673 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (27673 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ZSWIM7 ENST00000490395.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 37 publications found

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 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: STRONG Submitted by: King Faisal Specialist Hospital and Research Center
• ovarian dysgenesis 10

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• colorectal adenoma

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM7	NM_001042697.2	c.*1451G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000399277.6	NP_001036162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM7	ENST00000399277.6	c.*1451G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_001042697.2	ENSP00000382218.1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90612 AN: 151816 Hom.: 27622 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.586

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.597 AC: 90732 AN: 151934 Hom.: 27673 Cov.: 31 AF XY: 0.595 AC XY: 44183 AN XY: 74270

African (AFR) AF: 0.696 AC: 28841 AN: 41430

American (AMR) AF: 0.536 AC: 8184 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2321 AN: 3466

East Asian (EAS) AF: 0.267 AC: 1377 AN: 5148

South Asian (SAS) AF: 0.527 AC: 2539 AN: 4822

European-Finnish (FIN) AF: 0.607 AC: 6410 AN: 10558

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.576 AC: 39145 AN: 67942

Other (OTH) AF: 0.589 AC: 1240 AN: 2104

Alfa AF: 0.585 Hom.: 18929

Bravo AF: 0.592

Asia WGS AF: 0.462 AC: 1604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.15
DANN	Benign	0.44
PhyloP100		0.027
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1045599; hg19: chr17-15879910;