NM_001367799.1:c.1477C>T

Variant names:

• chr10-73792016-C-T
• rs201081141
• NM_001367799.1:c.1477C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001367799.1(ZSWIM8):​c.1477C>T​(p.Pro493Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000885 in 1,550,454 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (4 hom.)
• Consequence: ZSWIM8 NM_001367799.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032131046).
• BS2: High AC in GnomAd4 at 80 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.1477C>T	p.Pro493Ser	missense	Exon 10 of 26	NP_001354728.1	S4R410
	ZSWIM8	NM_001242488.2		c.1477C>T	p.Pro493Ser	missense	Exon 10 of 26	NP_001229417.1	A7E2V4-2
	ZSWIM8	NM_015037.4		c.1477C>T	p.Pro493Ser	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.1477C>T	p.Pro493Ser	missense	Exon 10 of 26	ENSP00000474944.1	S4R410
	ZSWIM8	ENST00000605216.5	TSL:1	c.1477C>T	p.Pro493Ser	missense	Exon 10 of 26	ENSP00000474748.1	A7E2V4-1
	ZSWIM8	ENST00000492395.5	TSL:1	n.334C>T		non_coding_transcript_exon	Exon 2 of 18	ENSP00000432423.1	H0YCW2

Frequencies

GnomAD3 genomes AF: 0.000525 AC: 80 AN: 152254 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000541 AC: 83 AN: 153438 AF XY: 0.000539

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000406

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000195

Gnomad NFE exome AF: 0.00128

Gnomad OTH exome AF: 0.000697

GnomAD4 exome AF: 0.000924 AC: 1292 AN: 1398200 Hom.: 4 Cov.: 32 AF XY: 0.000896 AC XY: 618 AN XY: 689408

African (AFR) AF: 0.0000317 AC: 1 AN: 31586

American (AMR) AF: 0.0000560 AC: 2 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35712

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.000184 AC: 9 AN: 48786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00116 AC: 1255 AN: 1078382

Other (OTH) AF: 0.000431 AC: 25 AN: 57942

GnomAD4 genome AF: 0.000525 AC: 80 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.000484 AC XY: 36 AN XY: 74384

African (AFR) AF: 0.000193 AC: 8 AN: 41468

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

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

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

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

European-Non Finnish (NFE) AF: 0.000926 AC: 63 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000880 Hom.: 0

Bravo AF: 0.000484

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000265 AC: 2

ExAC AF: 0.000219 AC: 18

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	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.081	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.28
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.036	D
Polyphen		0.56	P
Vest4		0.51
MVP		0.082
MPC		1.7
ClinPred		0.092	T
GERP RS		5.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.068
gMVP		0.61
Mutation Taster		=76/24	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: rs201081141; hg19: chr10-75551774; COSMIC: COSV105338097; COSMIC: COSV105338097;