Variant rs440454 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006929.5(SKIC2):c.126+165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 611,354 control chromosomes in the GnomAD database, including 175,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.78 ( 47012 hom., cov: 32)

Exomes 𝑓: 0.74 ( 128466 hom. )

Consequence

SKIC2
NM_006929.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.492

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 6-31959565-A-G is Benign according to our data. Variant chr6-31959565-A-G is described in ClinVar as [Benign]. Clinvar id is 1220566.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SKIC2	NM_006929.5 linkuse as main transcript	c.126+165A>G	intron_variant	ENST00000375394.7
SKIC2	XM_011514815.4 linkuse as main transcript	c.126+165A>G	intron_variant
SKIC2	XM_047419259.1 linkuse as main transcript	c.126+165A>G	intron_variant
SKIC2	XM_047419260.1 linkuse as main transcript	c.126+165A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC2	ENST00000375394.7 linkuse as main transcript	c.126+165A>G		intron_variant		1	NM_006929.5	P1

Frequencies

GnomAD3 genomes

AF:

0.780

AC:

118619

AN:

152060

Hom.:

46956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

0.848

Gnomad AMR

AF:

0.746

Gnomad ASJ

AF:

0.872

Gnomad EAS

AF:

0.679

Gnomad SAS

AF:

0.887

Gnomad FIN

AF:

0.741

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.710

Gnomad OTH

AF:

0.817

GnomAD4 exome

AF:

0.743

AC:

341035

AN:

459176

Hom.:

128466

Cov.:

AF XY:

0.753

AC XY:

183053

AN XY:

243254

show subpopulations

Gnomad4 AFR exome

AF:

0.908

Gnomad4 AMR exome

AF:

0.748

Gnomad4 ASJ exome

AF:

0.862

Gnomad4 EAS exome

AF:

0.649

Gnomad4 SAS exome

AF:

0.896

Gnomad4 FIN exome

AF:

0.722

Gnomad4 NFE exome

AF:

0.714

Gnomad4 OTH exome

AF:

0.749

GnomAD4 genome

AF:

0.780

AC:

118735

AN:

152178

Hom.:

47012

Cov.:

AF XY:

0.783

AC XY:

58232

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.906

Gnomad4 AMR

AF:

0.746

Gnomad4 ASJ

AF:

0.872

Gnomad4 EAS

AF:

0.679

Gnomad4 SAS

AF:

0.887

Gnomad4 FIN

AF:

0.741

Gnomad4 NFE

AF:

0.710

Gnomad4 OTH

AF:

0.819

Alfa

AF:

0.725

Hom.:

57888

Bravo

AF:

0.787

Asia WGS

AF:

0.844

AC:

2933

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.5

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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