Variant rs2303650 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014639.4(SKIC3):c.3888G>T(p.Arg1296Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,613,666 control chromosomes in the GnomAD database, including 24,529 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.22 ( 4659 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19870 hom. )

Consequence

SKIC3
NM_014639.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

SKIC3 (HGNC:23639): (SKI3 subunit of superkiller complex) This gene encodes a protein with twenty tetratricopeptide (TPR) repeats. Tetratricopeptide repeat containing motifs are found in a variety of proteins and may mediate protein-protein interactions and chaperone activity. Mutations in this gene are associated with trichohepatoenteric syndrome. [provided by RefSeq, Jul 2010]

SKIC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020938218).

BP6

Variant 5-95490951-C-A is Benign according to our data. Variant chr5-95490951-C-A is described in ClinVar as [Benign]. Clinvar id is 1166551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKIC3	NM_014639.4 linkuse as main transcript	c.3888G>T	p.Arg1296Ser	missense_variant	37/43	ENST00000358746.7
SKIC3	XM_047417937.1 linkuse as main transcript	c.3888G>T	p.Arg1296Ser	missense_variant	37/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC3	ENST00000358746.7 linkuse as main transcript	c.3888G>T	p.Arg1296Ser	missense_variant	37/43	1	NM_014639.4	P4

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33494

AN:

151882

Hom.:

4648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.226

GnomAD3 exomes

AF:

0.179

AC:

44893

AN:

251232

Hom.:

4818

AF XY:

0.177

AC XY:

24052

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.395

Gnomad AMR exome

AF:

0.166

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.123

Gnomad SAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.155

AC:

226758

AN:

1461666

Hom.:

19870

Cov.:

AF XY:

0.157

AC XY:

114319

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.395

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.327

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.117

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.221

AC:

33533

AN:

152000

Hom.:

4659

Cov.:

AF XY:

0.219

AC XY:

16312

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.388

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.326

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.150

Gnomad4 OTH

AF:

0.223

Alfa

AF:

0.169

Hom.:

6163

Bravo

AF:

0.233

TwinsUK

AF:

0.134

AC:

498

ALSPAC

AF:

0.128

AC:

493

ESP6500AA

AF:

0.374

AC:

1648

ESP6500EA

AF:

0.159

AC:

1367

ExAC

AF:

0.182

AC:

22103

Asia WGS

AF:

0.123

AC:

428

AN:

3478

EpiCase

AF:

0.170

EpiControl

AF:

0.170

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Trichohepatoenteric syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

.;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

0.12

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

.;N

REVEL

Benign

0.23

Sift

Benign

0.086

.;T

Sift4G

Benign

0.080

.;T

Polyphen

0.70

P;P

Vest4

0.24

MutPred

0.38

Gain of ubiquitination at K1295 (P = 0.0638);Gain of ubiquitination at K1295 (P = 0.0638);

MPC

0.19

ClinPred

0.022

GERP RS

3.2

Varity_R

0.27

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over