chr10-73797154-G-T

Variant names:

• chr10-73797154-G-T
• rs763410056
• NM_001367799.1:c.3316G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367799.1(ZSWIM8):​c.3316G>T​(p.Ala1106Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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)
• Consequence: ZSWIM8 NM_001367799.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.30
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1353873).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367799.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM8	NM_001367799.1	MANE Select	c.3316G>T	p.Ala1106Ser	missense	Exon 17 of 26	NP_001354728.1	S4R410
	ZSWIM8	NM_001242488.2		c.3301G>T	p.Ala1101Ser	missense	Exon 17 of 26	NP_001229417.1	A7E2V4-2
	ZSWIM8	NM_015037.4		c.3316G>T	p.Ala1106Ser	missense	Exon 17 of 26	NP_055852.2	A7E2V4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM8	ENST00000604729.6	TSL:5 MANE Select	c.3316G>T	p.Ala1106Ser	missense	Exon 17 of 26	ENSP00000474944.1	S4R410
	ZSWIM8	ENST00000605216.5	TSL:1	c.3301G>T	p.Ala1101Ser	missense	Exon 17 of 26	ENSP00000474748.1	A7E2V4-1
	ZSWIM8	ENST00000603187.5	TSL:1	c.1318G>T	p.Ala440Ser	missense	Exon 8 of 17	ENSP00000474766.1	S4R3U7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248584 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0066	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L
PhyloP100		6.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.062
Sift	Benign	0.40	T
Sift4G	Benign	0.80	T
Polyphen		0.0090	B
Vest4		0.37
MutPred		0.071		Gain of phosphorylation at A1101 (P = 0.0311)
MVP		0.043
MPC		0.73
ClinPred		0.22	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.11
gMVP		0.18
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs763410056; hg19: chr10-75556912;