chr10-73790196-C-T

Variant names:

• chr10-73790196-C-T
• rs746014099
• NM_001367799.1:c.845C>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.845C>T​(p.Ser282Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,613,222 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: ZSWIM8 NM_001367799.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.63
• Publications: 3 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=0.21376967).
• 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.845C>T	p.Ser282Leu	missense	Exon 7 of 26	NP_001354728.1	S4R410
	ZSWIM8	NM_001242488.2		c.845C>T	p.Ser282Leu	missense	Exon 7 of 26	NP_001229417.1	A7E2V4-2
	ZSWIM8	NM_015037.4		c.845C>T	p.Ser282Leu	missense	Exon 7 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.845C>T	p.Ser282Leu	missense	Exon 7 of 26	ENSP00000474944.1	S4R410
	ZSWIM8	ENST00000605216.5	TSL:1	c.845C>T	p.Ser282Leu	missense	Exon 7 of 26	ENSP00000474748.1	A7E2V4-1
	ZSWIM8	ENST00000398706.6	TSL:2	c.845C>T	p.Ser282Leu	missense	Exon 7 of 26	ENSP00000381693.2	A7E2V4-4

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 248422 AF XY: 0.0000223

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1461048 Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16 AN XY: 726776

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000306 AC: 34 AN: 1111526

Other (OTH) AF: 0.0000166 AC: 1 AN: 60346

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68030

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

Alfa AF: 0.0000580 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000248 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	0.44
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Benign	0.070
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.6
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.13
Sift	Benign	0.053	T
Sift4G	Benign	0.091	T
Polyphen		0.045	B
Vest4		0.44
MutPred		0.24		Loss of disorder (P = 0.0186)
MVP		0.068
MPC		2.5
ClinPred		0.55	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.41
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs746014099; hg19: chr10-75549954; COSMIC: COSV67133590; COSMIC: COSV67133590;