chr17-15999405-T-G

Variant names:

• chr17-15999405-T-G
• rs886052624
• NM_001042697.2:c.76+114A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042697.2(ZSWIM7):​c.76+114A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000853 in 1,172,082 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: 8.5e-7 (0 hom.)
• Consequence: ZSWIM7 NM_001042697.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.57
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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+114A>C		intron	N/A	NP_001036162.1	Q19AV6
	ZSWIM7	NM_001042698.2		c.76+114A>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+114A>C		intron	N/A	ENSP00000382218.1	Q19AV6
	ZSWIM7	ENST00000472495.5	TSL:1	c.76+114A>C		intron	N/A	ENSP00000419138.1	Q19AV6
	ZSWIM7	ENST00000486706.6	TSL:1	n.89+101A>C		intron	N/A	ENSP00000463327.1	J3QS31

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.53e-7 AC: 1 AN: 1172082 Hom.: 0 Cov.: 16 AF XY: 0.00000170 AC XY: 1 AN XY: 588446

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27402

American (AMR) AF: 0.00 AC: 0 AN: 35048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23304

East Asian (EAS) AF: 0.00 AC: 0 AN: 35490

South Asian (SAS) AF: 0.00 AC: 0 AN: 75900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3684

European-Non Finnish (NFE) AF: 0.00000113 AC: 1 AN: 886242

Other (OTH) AF: 0.00 AC: 0 AN: 50730

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.35
PhyloP100		-4.6
PromoterAI		0.15	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: rs886052624; hg19: chr17-15902719;