rs440454

Positions:

• chr6-31959565-A-G
• chr6-31959565-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.492

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 (HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKIC2	NM_006929.5	c.126+165A>G		intron_variant		ENST00000375394.7	NP_008860.4
SKIC2	XM_011514815.4	c.126+165A>G		intron_variant			XP_011513117.1
SKIC2	XM_047419259.1	c.126+165A>G		intron_variant			XP_047275215.1
SKIC2	XM_047419260.1	c.126+165A>G		intron_variant			XP_047275216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKIC2	ENST00000375394.7	c.126+165A>G		intron_variant		1	NM_006929.5	ENSP00000364543.2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118619 AN: 152060 Hom.: 46956 Cov.: 32

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.: 4 AF XY: 0.753 AC XY: 183053 AN XY: 243254

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.: 32 AF XY: 0.783 AC XY: 58232 AN XY: 74404

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

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

Other links and lift over

dbSNP: rs440454; hg19: chr6-31927342;