rs36038685

Positions:

chr6-31961960-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_006929.5(SKIC2):c.970C>T(p.Arg324Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,612,886 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 12 hom., cov: 32)

Exomes 𝑓: 0.012 ( 183 hom. )

Consequence

SKIC2
NM_006929.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.506

Variant links:

Genes affected

SKIC2 (HGNC:10898): (SKI2 subunit of superkiller complex) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is a human homologue of yeast SKI2 and may be involved in antiviral activity by blocking translation of poly(A) deficient mRNAs. This gene is located in the class III region of the major histocompatibility complex. [provided by RefSeq, Jul 2008]

SKIC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 6-31961960-C-T is Benign according to our data. Variant chr6-31961960-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 377168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-31961960-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1807/152322) while in subpopulation AFR AF= 0.0174 (725/41574). AF 95% confidence interval is 0.0164. There are 12 homozygotes in gnomad4. There are 800 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SKIC2	NM_006929.5 linkuse as main transcript	c.970C>T	p.Arg324Trp	missense_variant	10/28	ENST00000375394.7
SKIC2	XM_011514815.4 linkuse as main transcript	c.970C>T	p.Arg324Trp	missense_variant	10/25
SKIC2	XM_047419259.1 linkuse as main transcript	c.970C>T	p.Arg324Trp	missense_variant	10/25
SKIC2	XM_047419260.1 linkuse as main transcript	c.970C>T	p.Arg324Trp	missense_variant	10/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC2	ENST00000375394.7 linkuse as main transcript	c.970C>T	p.Arg324Trp	missense_variant	10/28	1	NM_006929.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1804

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00807

AC:

1990

AN:

246674

Hom.:

AF XY:

0.00807

AC XY:

1085

AN XY:

134456

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.00722

Gnomad ASJ exome

AF:

0.0238

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00161

Gnomad FIN exome

AF:

0.000740

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.00856

GnomAD4 exome

AF:

0.0124

AC:

18172

AN:

1460564

Hom.:

183

Cov.:

AF XY:

0.0121

AC XY:

8772

AN XY:

726624

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.00778

Gnomad4 ASJ exome

AF:

0.0233

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00189

Gnomad4 FIN exome

AF:

0.000650

Gnomad4 NFE exome

AF:

0.0138

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0119

AC:

1807

AN:

152322

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

800

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0174

Gnomad4 AMR

AF:

0.00771

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.0131

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0122

AC:

ESP6500AA

AF:

0.0165

AC:

ESP6500EA

AF:

0.0126

AC:

ExAC

AF:

0.00796

AC:

944

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	SKIC2: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 31, 2016	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Dec 10, 2021

- -

Trichohepatoenteric syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.12

MetaRNN

Benign

0.0091

MetaSVM

Benign

-0.44

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.29

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0080

Polyphen

0.96

Vest4

0.39

MVP

0.92

MPC

0.86

ClinPred

0.092

GERP RS

4.8

Varity_R

0.36

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 25

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