20-45883676-A-G

Variant names:

• chr20-45883676-A-G
• NM_080603.5:c.1084A>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.1084A>G​(p.Lys362Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 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: 6.8e-7 (0 hom.)
• Consequence: ZSWIM1 NM_080603.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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=0.08153683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM1	NM_080603.5	c.1084A>G	p.Lys362Glu	missense_variant	Exon 2 of 2	ENST00000372523.1	NP_542170.3
ZSWIM1	XM_005260610.6	c.1084A>G	p.Lys362Glu	missense_variant	Exon 2 of 2		XP_005260667.1
ZSWIM1	XM_005260611.5	c.1084A>G	p.Lys362Glu	missense_variant	Exon 2 of 2		XP_005260668.1
ZSWIM1	XM_011529100.3	c.1084A>G	p.Lys362Glu	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.1084A>G	p.Lys362Glu	missense_variant	Exon 2 of 2	2	NM_080603.5	ENSP00000361601.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

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

Dec 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1084A>G (p.K362E) alteration is located in exon 2 (coding exon 1) of the ZSWIM1 gene. This alteration results from a A to G substitution at nucleotide position 1084, causing the lysine (K) at amino acid position 362 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	0.13
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0038	T;T
Eigen	Benign	0.015
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.62	.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.070	N;N
REVEL	Benign	0.097
Sift	Benign	0.25	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.65	P;P
Vest4		0.27
MutPred		0.23		Loss of ubiquitination at K362 (P = 0.0067);Loss of ubiquitination at K362 (P = 0.0067);
MVP		0.24
MPC		0.40
ClinPred		0.46	T
GERP RS		5.3
Varity_R		0.12
gMVP		0.32

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: chr20-44512315;