17-15987289-G-T

Variant names:

• chr17-15987289-G-T
• NM_001042697.2:c.178C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001042697.2(ZSWIM7):​c.178C>A​(p.Pro60Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSWIM7 NM_001042697.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.47

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM7	NM_001042697.2	c.178C>A	p.Pro60Thr	missense_variant	Exon 3 of 5	ENST00000399277.6	NP_001036162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM7	ENST00000399277.6	c.178C>A	p.Pro60Thr	missense_variant	Exon 3 of 5	1	NM_001042697.2	ENSP00000382218.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.178C>A (p.P60T) alteration is located in exon 3 (coding exon 3) of the ZSWIM7 gene. This alteration results from a C to A substitution at nucleotide position 178, causing the proline (P) at amino acid position 60 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Benign	0.95
DEOGEN2	Benign	0.36	T;T;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Uncertain	-0.093	T
MutationAssessor	Uncertain	2.6	M;.;M
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-7.1	D;.;D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;.;D
Sift4G	Benign	0.12	T;D;T
Polyphen		1.0	D;.;D
Vest4		0.67
MutPred		0.27		Loss of glycosylation at P60 (P = 0.0445);.;Loss of glycosylation at P60 (P = 0.0445);
MVP		0.41
MPC		0.66
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.84
gMVP		0.57

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-15890603;