rs410851

Positions:

chr6-31968891-T-C

Variant summary

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

The ENST00000375394.7(SKIC2):c.3201T>C(p.Tyr1067=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,612,252 control chromosomes in the GnomAD database, including 434,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48995 hom., cov: 32)

Exomes 𝑓: 0.72 ( 385106 hom. )

Consequence

SKIC2
ENST00000375394.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.97

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 (BayesDel_noAF=-0.93).

BP6

Variant 6-31968891-T-C is Benign according to our data. Variant chr6-31968891-T-C is described in ClinVar as [Benign]. Clinvar id is 356345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-31968891-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKIC2	NM_006929.5 linkuse as main transcript	c.3201T>C	p.Tyr1067=	synonymous_variant	26/28	ENST00000375394.7	NP_008860.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKIC2	ENST00000375394.7 linkuse as main transcript	c.3201T>C	p.Tyr1067=	synonymous_variant	26/28	1	NM_006929.5	ENSP00000364543	P1

Frequencies

GnomAD3 genomes

AF:

0.796

AC:

121010

AN:

152034

Hom.:

48928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.920

Gnomad AMI

AF:

0.848

Gnomad AMR

AF:

0.848

Gnomad ASJ

AF:

0.873

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.889

Gnomad FIN

AF:

0.748

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.712

Gnomad OTH

AF:

0.832

GnomAD3 exomes

AF:

0.781

AC:

192300

AN:

246250

Hom.:

76214

AF XY:

0.785

AC XY:

105395

AN XY:

134272

show subpopulations

Gnomad AFR exome

AF:

0.928

Gnomad AMR exome

AF:

0.852

Gnomad ASJ exome

AF:

0.872

Gnomad EAS exome

AF:

0.689

Gnomad SAS exome

AF:

0.901

Gnomad FIN exome

AF:

0.740

Gnomad NFE exome

AF:

0.720

Gnomad OTH exome

AF:

0.778

GnomAD4 exome

AF:

0.721

AC:

1053079

AN:

1460100

Hom.:

385106

Cov.:

AF XY:

0.728

AC XY:

528442

AN XY:

726350

show subpopulations

Gnomad4 AFR exome

AF:

0.927

Gnomad4 AMR exome

AF:

0.853

Gnomad4 ASJ exome

AF:

0.868

Gnomad4 EAS exome

AF:

0.689

Gnomad4 SAS exome

AF:

0.897

Gnomad4 FIN exome

AF:

0.732

Gnomad4 NFE exome

AF:

0.691

Gnomad4 OTH exome

AF:

0.743

GnomAD4 genome

AF:

0.796

AC:

121137

AN:

152152

Hom.:

48995

Cov.:

AF XY:

0.801

AC XY:

59549

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.920

Gnomad4 AMR

AF:

0.848

Gnomad4 ASJ

AF:

0.873

Gnomad4 EAS

AF:

0.684

Gnomad4 SAS

AF:

0.889

Gnomad4 FIN

AF:

0.748

Gnomad4 NFE

AF:

0.712

Gnomad4 OTH

AF:

0.834

Alfa

AF:

0.736

Hom.:

65554

Bravo

AF:

0.808

Asia WGS

AF:

0.851

AC:

2960

AN:

3478

EpiCase

AF:

0.745

EpiControl

AF:

0.763

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Trichohepatoenteric syndrome 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0090

DANN

Benign

0.58

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

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