rs60636875

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-15999502-C-A
• chr17-15999502-C-G
• chr17-15999502-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001042697.2(ZSWIM7):​c.76+17G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 1,596,822 control chromosomes in the GnomAD database, including 502 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (265 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (237 hom.)
• Consequence: ZSWIM7 NM_001042697.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.093).
• BP6: Variant 17-15999502-C-A is Benign according to our data. Variant chr17-15999502-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM7	NM_001042697.2	MANE Select	c.76+17G>T		intron	N/A	NP_001036162.1	Q19AV6
	ZSWIM7	NM_001042698.2		c.76+17G>T		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>T		intron	N/A	ENSP00000382218.1	Q19AV6
	ZSWIM7	ENST00000472495.5	TSL:1	c.76+17G>T		intron	N/A	ENSP00000419138.1	Q19AV6
	ZSWIM7	ENST00000486706.6	TSL:1	n.89+4G>T		splice_region intron	N/A	ENSP00000463327.1	J3QS31

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4878 AN: 152190 Hom.: 261 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0230

GnomAD2 exomes AF: 0.00782 AC: 1690 AN: 215988 AF XY: 0.00554

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.00544

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000470

Gnomad OTH exome AF: 0.00512

GnomAD4 exome AF: 0.00345 AC: 4990 AN: 1444514 Hom.: 237 Cov.: 31 AF XY: 0.00297 AC XY: 2137 AN XY: 718752

African (AFR) AF: 0.117 AC: 3889 AN: 33328

American (AMR) AF: 0.00646 AC: 287 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26018

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

South Asian (SAS) AF: 0.000210 AC: 18 AN: 85710

European-Finnish (FIN) AF: 0.0000245 AC: 1 AN: 40856

Middle Eastern (MID) AF: 0.00598 AC: 30 AN: 5018

European-Non Finnish (NFE) AF: 0.000224 AC: 249 AN: 1109688

Other (OTH) AF: 0.00860 AC: 515 AN: 59892

GnomAD4 genome AF: 0.0322 AC: 4900 AN: 152308 Hom.: 265 Cov.: 32 AF XY: 0.0306 AC XY: 2281 AN XY: 74478

African (AFR) AF: 0.112 AC: 4636 AN: 41568

American (AMR) AF: 0.0120 AC: 184 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68022

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0133 Hom.: 39

Bravo AF: 0.0369

Asia WGS AF: 0.00520 AC: 20 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Mitochondrial complex III deficiency nuclear type 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.5
DANN	Benign	0.91
PhyloP100		-0.11
PromoterAI		-0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=97/3	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: rs60636875; hg19: chr17-15902816; COSMIC: COSV55422995; COSMIC: COSV55422995;