rs438999

chr6-31960529-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_006929.5(SKIC2):c.452A>G(p.Gln151Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 1,611,646 control chromosomes in the GnomAD database, including 8,980 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1234 hom., cov: 32)

Exomes 𝑓: 0.098 ( 7746 hom. )

Consequence

SKIC2
NM_006929.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 7.65

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 -15 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 6-31960529-A-G is Benign according to our data. Variant chr6-31960529-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 356316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SKIC2	NM_006929.5 linkuse as main transcript	c.452A>G	p.Gln151Arg	missense_variant	5/28	ENST00000375394.7
SKIC2	XM_011514815.4 linkuse as main transcript	c.452A>G	p.Gln151Arg	missense_variant	5/25
SKIC2	XM_047419259.1 linkuse as main transcript	c.452A>G	p.Gln151Arg	missense_variant	5/25
SKIC2	XM_047419260.1 linkuse as main transcript	c.452A>G	p.Gln151Arg	missense_variant	5/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC2	ENST00000375394.7 linkuse as main transcript	c.452A>G	p.Gln151Arg	missense_variant	5/28	1	NM_006929.5	P1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17857

AN:

151898

Hom.:

1235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.0463

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.0624

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.0577

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0911

Gnomad OTH

AF:

0.131

GnomAD3 exomes

AF:

0.0970

AC:

24386

AN:

251370

Hom.:

1423

AF XY:

0.0994

AC XY:

13512

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.0708

Gnomad ASJ exome

AF:

0.0520

Gnomad EAS exome

AF:

0.0619

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.0635

Gnomad NFE exome

AF:

0.0910

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0978

AC:

142765

AN:

1459630

Hom.:

7746

Cov.:

AF XY:

0.0986

AC XY:

71647

AN XY:

726286

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.0742

Gnomad4 ASJ exome

AF:

0.0553

Gnomad4 EAS exome

AF:

0.0737

Gnomad4 SAS exome

AF:

0.149

Gnomad4 FIN exome

AF:

0.0651

Gnomad4 NFE exome

AF:

0.0950

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.118

AC:

17879

AN:

152016

Hom.:

1234

Cov.:

AF XY:

0.115

AC XY:

8583

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.0573

Gnomad4 EAS

AF:

0.0624

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.0577

Gnomad4 NFE

AF:

0.0911

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.0900

Hom.:

1555

Bravo

AF:

0.125

TwinsUK

AF:

0.0949

AC:

352

ALSPAC

AF:

0.104

AC:

402

ESP6500AA

AF:

0.184

AC:

809

ESP6500EA

AF:

0.0880

AC:

757

ExAC

AF:

0.0997

AC:

12107

Asia WGS

AF:

0.156

AC:

539

AN:

3478

EpiCase

AF:

0.0870

EpiControl

AF:

0.0885

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Trichohepatoenteric syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.042

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.95

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.095

P;P

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.74

REVEL

Benign

0.047

Sift

Benign

0.068

Sift4G

Benign

0.12

Polyphen

0.039

Vest4

0.098

MPC

0.43

ClinPred

0.038

GERP RS

5.1

Varity_R

0.22

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.53

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.53

Position offset: 0

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