NM_001367799.1:c.1528C>T

Variant names:

• chr10-73792067-C-T
• rs762336991
• NM_001367799.1:c.1528C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001367799.1(ZSWIM8):​c.1528C>T​(p.Arg510Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000526 in 1,539,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R510Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: ZSWIM8 NM_001367799.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.118062615).
• BS2: High AC in GnomAd4 at 7 AD gene.

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.1528C>T	p.Arg510Trp	missense	Exon 10 of 26	NP_001354728.1	S4R410
	ZSWIM8	NM_001242488.2		c.1528C>T	p.Arg510Trp	missense	Exon 10 of 26	NP_001229417.1	A7E2V4-2
	ZSWIM8	NM_015037.4		c.1528C>T	p.Arg510Trp	missense	Exon 10 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.1528C>T	p.Arg510Trp	missense	Exon 10 of 26	ENSP00000474944.1	S4R410
	ZSWIM8	ENST00000605216.5	TSL:1	c.1528C>T	p.Arg510Trp	missense	Exon 10 of 26	ENSP00000474748.1	A7E2V4-1
	ZSWIM8	ENST00000492395.5	TSL:1	n.385C>T		non_coding_transcript_exon	Exon 2 of 18	ENSP00000432423.1	H0YCW2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000535 AC: 8 AN: 149672 AF XY: 0.0000624

Gnomad AFR exome AF: 0.000266

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000925

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000524

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000534 AC: 74 AN: 1386776 Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 30 AN XY: 681466

African (AFR) AF: 0.0000638 AC: 2 AN: 31364

American (AMR) AF: 0.00 AC: 0 AN: 35016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24834

East Asian (EAS) AF: 0.0000282 AC: 1 AN: 35458

South Asian (SAS) AF: 0.0000507 AC: 4 AN: 78950

European-Finnish (FIN) AF: 0.0000207 AC: 1 AN: 48366

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5620

European-Non Finnish (NFE) AF: 0.0000542 AC: 58 AN: 1069908

Other (OTH) AF: 0.000122 AC: 7 AN: 57260

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74372

African (AFR) AF: 0.0000723 AC: 3 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000700 Hom.: 0

Bravo AF: 0.0000529

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000478 AC: 5

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.0
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.41		Loss of disorder (P = 0.0163)
MVP		0.22
MPC		2.5
ClinPred		0.22	T
GERP RS		5.5
PromoterAI		0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.15
gMVP		0.74
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs762336991; hg19: chr10-75551825; COSMIC: COSV101290209; COSMIC: COSV101290209;