rs106287

Positions:

chr6-31967973-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000375394.7(SKIC2):c.2749G>A(p.Val917Met) variant causes a missense change. The variant allele was found at a frequency of 0.0307 in 1,613,070 control chromosomes in the GnomAD database, including 978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 56 hom., cov: 32)

Exomes 𝑓: 0.032 ( 922 hom. )

Consequence

SKIC2
ENST00000375394.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.38

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=0.0037950873).

BP6

Variant 6-31967973-G-A is Benign according to our data. Variant chr6-31967973-G-A is described in ClinVar as [Benign]. Clinvar id is 356342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0207 (3149/152344) while in subpopulation AMR AF= 0.0376 (576/15308). AF 95% confidence interval is 0.0351. There are 56 homozygotes in gnomad4. There are 1403 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SKIC2	NM_006929.5 linkuse as main transcript	c.2749G>A	p.Val917Met	missense_variant	23/28	ENST00000375394.7	NP_008860.4
SKIC2	XM_011514815.4 linkuse as main transcript	c.2749G>A	p.Val917Met	missense_variant	23/25		XP_011513117.1
SKIC2	XM_047419259.1 linkuse as main transcript	c.2749G>A	p.Val917Met	missense_variant	23/25		XP_047275215.1
SKIC2	XM_047419260.1 linkuse as main transcript	c.2749G>A	p.Val917Met	missense_variant	23/24		XP_047275216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKIC2	ENST00000375394.7 linkuse as main transcript	c.2749G>A	p.Val917Met	missense_variant	23/28	1	NM_006929.5	ENSP00000364543	P1

Frequencies

GnomAD3 genomes

AF:

0.0207

AC:

3148

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00712

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0376

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00263

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0313

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0184

AC:

4541

AN:

246340

Hom.:

AF XY:

0.0181

AC XY:

2434

AN XY:

134318

show subpopulations

Gnomad AFR exome

AF:

0.00543

Gnomad AMR exome

AF:

0.0259

Gnomad ASJ exome

AF:

0.0120

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000658

Gnomad FIN exome

AF:

0.00375

Gnomad NFE exome

AF:

0.0289

Gnomad OTH exome

AF:

0.0275

GnomAD4 exome

AF:

0.0318

AC:

46450

AN:

1460726

Hom.:

922

Cov.:

AF XY:

0.0303

AC XY:

22010

AN XY:

726674

show subpopulations

Gnomad4 AFR exome

AF:

0.00517

Gnomad4 AMR exome

AF:

0.0269

Gnomad4 ASJ exome

AF:

0.0132

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00417

Gnomad4 NFE exome

AF:

0.0386

Gnomad4 OTH exome

AF:

0.0266

GnomAD4 genome

AF:

0.0207

AC:

3149

AN:

152344

Hom.:

Cov.:

AF XY:

0.0188

AC XY:

1403

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00710

Gnomad4 AMR

AF:

0.0376

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00263

Gnomad4 NFE

AF:

0.0313

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0261

Hom.:

116

Bravo

AF:

0.0242

TwinsUK

AF:

0.0405

AC:

150

ALSPAC

AF:

0.0480

AC:

185

ESP6500AA

AF:

0.00563

AC:

ESP6500EA

AF:

0.0336

AC:

182

ExAC

AF:

0.0163

AC:

1923

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0304

EpiControl

AF:

0.0298

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Trichohepatoenteric syndrome 2

Benign:1

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:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.8

REVEL

Benign

0.20

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.091

MPC

1.1

ClinPred

0.016

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.085

gMVP

0.63

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