17-15999502-C-G

Variant names:

• chr17-15999502-C-G
• rs60636875
• NM_001042697.2:c.76+17G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042697.2(ZSWIM7):​c.76+17G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,516 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZSWIM7 NM_001042697.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 5 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.114).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM7	NM_001042697.2	MANE Select	c.76+17G>C		intron	N/A	NP_001036162.1	Q19AV6
	ZSWIM7	NM_001042698.2		c.76+17G>C		intron	N/A	NP_001036163.1	Q19AV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM7	ENST00000399277.6	TSL:1 MANE Select	c.76+17G>C		intron	N/A	ENSP00000382218.1	Q19AV6
	ZSWIM7	ENST00000472495.5	TSL:1	c.76+17G>C		intron	N/A	ENSP00000419138.1	Q19AV6
	ZSWIM7	ENST00000486706.6	TSL:1	n.89+4G>C		splice_region intron	N/A	ENSP00000463327.1	J3QS31

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 215988 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444516 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718752

African (AFR) AF: 0.00 AC: 0 AN: 33330

American (AMR) AF: 0.00 AC: 0 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 85710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5018

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109688

Other (OTH) AF: 0.00 AC: 0 AN: 59892

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.7
DANN	Benign	0.95
PhyloP100		-0.11
PromoterAI		-0.098	Neutral

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: rs60636875; hg19: chr17-15902816;