17-15977837-C-G

Variant names:

• chr17-15977837-C-G
• rs11654
• ENST00000486706.6:n.*643G>C

Variant summary

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

The ENST00000486706.6(ZSWIM7):​n.*643G>C 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 0.565 in 449,866 control chromosomes in the GnomAD database, including 74,538 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 (27865 hom., cov: 31)
  • Exomes 𝑓: 0.55 (46673 hom.)
• Consequence: ZSWIM7 ENST00000486706.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 15 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=-0.9).
• 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: ENST00000486706.6. 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.*210G>C		3_prime_UTR	Exon 5 of 5	NP_001036162.1
	ZSWIM7	NM_001042698.2		c.*80G>C		3_prime_UTR	Exon 6 of 6	NP_001036163.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM7	ENST00000486706.6	TSL:1	n.*643G>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000463327.1
	ZSWIM7	ENST00000490395.5	TSL:1	n.*420G>C		non_coding_transcript_exon	Exon 6 of 8	ENSP00000464605.1
	ZSWIM7	ENST00000585208.5	TSL:1	n.*747G>C		non_coding_transcript_exon	Exon 8 of 8	ENSP00000464227.1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90938 AN: 151870 Hom.: 27814 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.547 AC: 163010 AN: 297878 Hom.: 46673 Cov.: 3 AF XY: 0.548 AC XY: 84641 AN XY: 154510

African (AFR) AF: 0.696 AC: 6941 AN: 9978

American (AMR) AF: 0.491 AC: 7086 AN: 14440

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 6545 AN: 9648

East Asian (EAS) AF: 0.244 AC: 6007 AN: 24570

South Asian (SAS) AF: 0.523 AC: 11399 AN: 21800

European-Finnish (FIN) AF: 0.588 AC: 11106 AN: 18876

Middle Eastern (MID) AF: 0.634 AC: 824 AN: 1300

European-Non Finnish (NFE) AF: 0.574 AC: 102933 AN: 179302

Other (OTH) AF: 0.566 AC: 10169 AN: 17964

GnomAD4 genome AF: 0.599 AC: 91058 AN: 151988 Hom.: 27865 Cov.: 31 AF XY: 0.597 AC XY: 44335 AN XY: 74272

African (AFR) AF: 0.697 AC: 28902 AN: 41474

American (AMR) AF: 0.539 AC: 8218 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2366 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1389 AN: 5166

South Asian (SAS) AF: 0.528 AC: 2541 AN: 4810

European-Finnish (FIN) AF: 0.607 AC: 6402 AN: 10544

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39315 AN: 67950

Other (OTH) AF: 0.592 AC: 1250 AN: 2112

Alfa AF: 0.450 Hom.: 1134

Bravo AF: 0.595

Asia WGS AF: 0.463 AC: 1608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.47
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs11654; hg19: chr17-15881151; COSMIC: COSV58481774; COSMIC: COSV58481774;