10-73799290-G-T

Variant names:

• chr10-73799290-G-T
• NM_001367799.1:c.4465G>T

Variant summary

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

The NM_001367799.1(ZSWIM8):​c.4465G>T​(p.Val1489Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,924 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZSWIM8 NM_001367799.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.06

Genes affected

ZSWIM8 (HGNC:23528): (zinc finger SWIM-type containing 8) Enables ubiquitin ligase-substrate adaptor activity. Involved in positive regulation of miRNA catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ZSWIM8-AS1 (HGNC:45103): (ZSWIM8 antisense RNA 1)

ENSG00000272916 (HGNC:):

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
ZSWIM8	NM_001367799.1	c.4465G>T	p.Val1489Phe	missense_variant	Exon 21 of 26	ENST00000604729.6	NP_001354728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM8	ENST00000604729.6	c.4465G>T	p.Val1489Phe	missense_variant	Exon 21 of 26	5	NM_001367799.1	ENSP00000474944.1
ENSG00000272916	ENST00000603027.5	n.*1432+1213C>A		intron_variant	Intron 15 of 16	2		ENSP00000475031.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449924 Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1 AN XY: 720306

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: 9.04e-7

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	0.0035	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;.;.;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.0	.;.;.;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.8	.;.;N;.
REVEL	Benign	0.28
Sift	Uncertain	0.016	.;.;D;.
Sift4G	Benign	0.34	T;T;T;T
Polyphen		1.0	.;.;D;D
Vest4		0.60
MutPred		0.43		.;.;.;Loss of disorder (P = 0.0795);
MVP		0.043
MPC		0.71
ClinPred		0.89	D
GERP RS		5.0
Varity_R		0.28
gMVP		0.70

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: chr10-75559048;