NM_006929.5:c.3212C>T

Variant names:

Variant summary

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

The NM_006929.5(SKIC2):c.3212C>T(p.Ala1071Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,612,372 control chromosomes in the GnomAD database, including 19,202 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3497 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15705 hom. )

Consequence

SKIC2
NM_006929.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.53

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051842034).

BP6

Variant 6-31968902-C-T is Benign according to our data. Variant chr6-31968902-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 356346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIC2	NM_006929.5 link	c.3212C>T	p.Ala1071Val	missense_variant	Exon 26 of 28	ENST00000375394.7	NP_008860.4	Q15477A0A1U9X8J1
SKIC2	XM_011514815.4 link	c.*234C>T		downstream_gene_variant			XP_011513117.1	A0A8V8TLC0
SKIC2	XM_047419259.1 link	c.*253C>T		downstream_gene_variant			XP_047275215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIC2	ENST00000375394.7 link	c.3212C>T	p.Ala1071Val	missense_variant	Exon 26 of 28	1	NM_006929.5	ENSP00000364543.2		Q15477

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28640

AN:

152026

Hom.:

3490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.0983

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.0674

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.208

GnomAD3 exomes

AF:

0.145

AC:

35689

AN:

246308

Hom.:

3288

AF XY:

0.147

AC XY:

19767

AN XY:

134286

show subpopulations

Gnomad AFR exome

AF:

0.342

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.0990

Gnomad EAS exome

AF:

0.102

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.0710

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.138

AC:

201749

AN:

1460228

Hom.:

15705

Cov.:

AF XY:

0.140

AC XY:

101366

AN XY:

726416

show subpopulations

Gnomad4 AFR exome

AF:

0.347

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.0981

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.0743

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.189

AC:

28680

AN:

152144

Hom.:

3497

Cov.:

AF XY:

0.186

AC XY:

13834

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.341

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.0983

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.0674

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.206

Alfa

AF:

0.131

Hom.:

2560

Bravo

AF:

0.204

TwinsUK

AF:

0.128

AC:

474

ALSPAC

AF:

0.141

AC:

545

ESP6500AA

AF:

0.314

AC:

947

ESP6500EA

AF:

0.124

AC:

670

ExAC

AF:

0.149

AC:

17562

Asia WGS

AF:

0.223

AC:

777

AN:

3478

EpiCase

AF:

0.127

EpiControl

AF:

0.130

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

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Dec 03, 2021

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Trichohepatoenteric syndrome 2

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.037

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.25

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.1

REVEL

Benign

0.12

Sift

Benign

0.30

Sift4G

Benign

0.28

Polyphen

0.98

Vest4

0.052

MPC

0.38

ClinPred

0.010

GERP RS

1.7

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.045

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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