17-15987334-C-T

Variant names:

• chr17-15987334-C-T
• NM_001042697.2:c.133G>A

Variant summary

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

The NM_001042697.2(ZSWIM7):​c.133G>A​(p.Ala45Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,266 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZSWIM7 NM_001042697.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.133G>A	p.Ala45Thr	missense	Exon 3 of 5	NP_001036162.1	Q19AV6
	ZSWIM7	NM_001042698.2		c.133G>A	p.Ala45Thr	missense	Exon 3 of 6	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.133G>A	p.Ala45Thr	missense	Exon 3 of 5	ENSP00000382218.1	Q19AV6
	ZSWIM7	ENST00000472495.5	TSL:1	c.133G>A	p.Ala45Thr	missense	Exon 3 of 6	ENSP00000419138.1	Q19AV6
	ZSWIM7	ENST00000486706.6	TSL:1	n.*50G>A		non_coding_transcript_exon	Exon 3 of 6	ENSP00000463327.1	J3QS31

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461266 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726942

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111752

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Uncertain	0.50	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.92
MutPred		0.27		Loss of helix (P = 0.0444)
MVP		0.35
MPC		0.61
ClinPred		0.96	D
GERP RS		5.9
Varity_R		0.54
gMVP		0.80
Mutation Taster		=71/29	polymorphism

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

hg19: chr17-15890648;