20-45882782-C-G

Variant names:

• chr20-45882782-C-G
• NM_080603.5:c.190C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_080603.5(ZSWIM1):​c.190C>G​(p.Gln64Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZSWIM1 NM_080603.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55

Genes affected

ZSWIM1 (HGNC:16155): (zinc finger SWIM-type containing 1) Predicted to enable zinc ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.788

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM1	NM_080603.5	c.190C>G	p.Gln64Glu	missense_variant	Exon 2 of 2	ENST00000372523.1	NP_542170.3
ZSWIM1	XM_005260610.6	c.190C>G	p.Gln64Glu	missense_variant	Exon 2 of 2		XP_005260667.1
ZSWIM1	XM_005260611.5	c.190C>G	p.Gln64Glu	missense_variant	Exon 2 of 2		XP_005260668.1
ZSWIM1	XM_011529100.3	c.190C>G	p.Gln64Glu	missense_variant	Exon 2 of 2		XP_011527402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM1	ENST00000372523.1	c.190C>G	p.Gln64Glu	missense_variant	Exon 2 of 2	2	NM_080603.5	ENSP00000361601.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.190C>G (p.Q64E) alteration is located in exon 2 (coding exon 1) of the ZSWIM1 gene. This alteration results from a C to G substitution at nucleotide position 190, causing the glutamine (Q) at amino acid position 64 to be replaced by a glutamic acid (E). 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	0.22
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.79
MutPred		0.62		Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP		0.71
MPC		0.77
ClinPred		0.93	D
GERP RS		5.3
Varity_R		0.56
gMVP		0.85

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: chr20-44511421;