rs454212

chr6-31966595-C-T

Variant summary

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

The NM_006929.5(SKIC2):c.2203-114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,092,476 control chromosomes in the GnomAD database, including 13,752 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3485 hom., cov: 32)
  • Exomes 𝑓: 0.14 (10267 hom.)
• Consequence: SKIC2 NM_006929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKIC2	NM_006929.5	c.2203-114C>T		intron_variant		ENST00000375394.7
SKIC2	XM_011514815.4	c.2203-114C>T		intron_variant
SKIC2	XM_047419259.1	c.2203-114C>T		intron_variant
SKIC2	XM_047419260.1	c.2203-114C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC2	ENST00000375394.7	c.2203-114C>T		intron_variant		1	NM_006929.5	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28585 AN: 151864 Hom.: 3478 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0986

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.138 AC: 129780 AN: 940496 Hom.: 10267 AF XY: 0.140 AC XY: 66888 AN XY: 479216

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0991

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.0742

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.188 AC: 28623 AN: 151980 Hom.: 3485 Cov.: 32 AF XY: 0.186 AC XY: 13808 AN XY: 74292

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0987

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.0674

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.207

Alfa AF: 0.137 Hom.: 1614

Bravo AF: 0.204

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.9
Dann	Benign	0.73

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: rs454212; hg19: chr6-31934372; COSMIC: COSV61713437; COSMIC: COSV61713437;