17-15980913-A-G

Variant names:

• chr17-15980913-A-G
• rs2286796
• NM_001042697.2:c.306+127T>C

Variant summary

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

The NM_001042697.2(ZSWIM7):​c.306+127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 617,924 control chromosomes in the GnomAD database, including 104,911 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 (27968 hom., cov: 31)
  • Exomes 𝑓: 0.56 (76943 hom.)
• Consequence: ZSWIM7 NM_001042697.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 18 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042697.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM7	NM_001042697.2	MANE Select	c.306+127T>C		intron	N/A	NP_001036162.1
	ZSWIM7	NM_001042698.2		c.306+127T>C		intron	N/A	NP_001036163.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM7	ENST00000399277.6	TSL:1 MANE Select	c.306+127T>C		intron	N/A	ENSP00000382218.1
	ZSWIM7	ENST00000472495.5	TSL:1	c.306+127T>C		intron	N/A	ENSP00000419138.1
	ZSWIM7	ENST00000486706.6	TSL:1	n.*316+127T>C		intron	N/A	ENSP00000463327.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91123 AN: 151928 Hom.: 27915 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.564 AC: 262870 AN: 465878 Hom.: 76943 AF XY: 0.564 AC XY: 135057 AN XY: 239330

African (AFR) AF: 0.706 AC: 9299 AN: 13174

American (AMR) AF: 0.496 AC: 8505 AN: 17154

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 8231 AN: 12106

East Asian (EAS) AF: 0.246 AC: 7172 AN: 29150

South Asian (SAS) AF: 0.554 AC: 16810 AN: 30362

European-Finnish (FIN) AF: 0.603 AC: 16916 AN: 28066

Middle Eastern (MID) AF: 0.638 AC: 2058 AN: 3224

European-Non Finnish (NFE) AF: 0.583 AC: 179575 AN: 307896

Other (OTH) AF: 0.578 AC: 14304 AN: 24746

GnomAD4 genome AF: 0.600 AC: 91245 AN: 152046 Hom.: 27968 Cov.: 31 AF XY: 0.598 AC XY: 44443 AN XY: 74304

African (AFR) AF: 0.697 AC: 28881 AN: 41440

American (AMR) AF: 0.541 AC: 8263 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2364 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1389 AN: 5168

South Asian (SAS) AF: 0.531 AC: 2564 AN: 4826

European-Finnish (FIN) AF: 0.608 AC: 6422 AN: 10566

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.580 AC: 39433 AN: 67986

Other (OTH) AF: 0.593 AC: 1250 AN: 2108

Alfa AF: 0.592 Hom.: 3306

Bravo AF: 0.596

Asia WGS AF: 0.466 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.60
PhyloP100		-0.20
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: rs2286796; hg19: chr17-15884227; COSMIC: COSV67886921; COSMIC: COSV67886921;