rs429608

chr6-31962685-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006929.5(SKIC2):c.1212-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,607,370 control chromosomes in the GnomAD database, including 19,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.16 (2093 hom., cov: 31)
  • Exomes 𝑓: 0.15 (17847 hom.)
• Consequence: SKIC2 NM_006929.5 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.34

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKIC2	NM_006929.5	c.1212-29G>A		intron_variant		ENST00000375394.7
SKIC2	XM_011514815.4	c.1212-29G>A		intron_variant
SKIC2	XM_047419259.1	c.1212-29G>A		intron_variant
SKIC2	XM_047419260.1	c.1212-29G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC2	ENST00000375394.7	c.1212-29G>A		intron_variant		1	NM_006929.5	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24462 AN: 151900 Hom.: 2093 Cov.: 31

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.0837

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.143 AC: 35468 AN: 248358 Hom.: 2828 AF XY: 0.148 AC XY: 19884 AN XY: 134760

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.0989

Gnomad ASJ exome AF: 0.0919

Gnomad EAS exome AF: 0.0779

Gnomad SAS exome AF: 0.218

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.153 AC: 222530 AN: 1455352 Hom.: 17847 Cov.: 31 AF XY: 0.154 AC XY: 111637 AN XY: 724432

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.0951

Gnomad4 EAS exome AF: 0.0949

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.161 AC: 24489 AN: 152018 Hom.: 2093 Cov.: 31 AF XY: 0.159 AC XY: 11810 AN XY: 74310

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.0839

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.166

Alfa AF: 0.139 Hom.: 3004

Bravo AF: 0.164

Asia WGS AF: 0.199 AC: 689 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

not provided

Department of Ophthalmology and Visual Sciences Kyoto University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	12
Dann	Benign	0.78

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

Other links and lift over

dbSNP: rs429608; hg19: chr6-31930462;