chr20-45883665-C-G

Position:

• chr20-45883665-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080603.5(ZSWIM1):​c.1073C>G​(p.Ser358Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZSWIM1 NM_080603.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08463648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSWIM1	NM_080603.5	c.1073C>G	p.Ser358Cys	missense_variant	2/2	ENST00000372523.1	NP_542170.3
ZSWIM1	XM_005260610.6	c.1073C>G	p.Ser358Cys	missense_variant	2/2		XP_005260667.1
ZSWIM1	XM_005260611.5	c.1073C>G	p.Ser358Cys	missense_variant	2/2		XP_005260668.1
ZSWIM1	XM_011529100.3	c.1073C>G	p.Ser358Cys	missense_variant	2/2		XP_011527402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSWIM1	ENST00000372523.1	c.1073C>G	p.Ser358Cys	missense_variant	2/2	2	NM_080603.5	ENSP00000361601.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461882 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.1073C>G (p.S358C) 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 1073, causing the serine (S) at amino acid position 358 to be replaced by a cysteine (C). 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	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0065	T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.47	.;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	0.96	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.85	N;N
REVEL	Benign	0.049
Sift	Benign	0.13	T;T
Sift4G	Uncertain	0.013	D;D
Polyphen		0.020	B;B
Vest4		0.099
MutPred		0.28		Loss of disorder (P = 0.0053);Loss of disorder (P = 0.0053);
MVP		0.19
MPC		0.18
ClinPred		0.13	T
GERP RS		4.3
Varity_R		0.083
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs1449266246; hg19: chr20-44512304;