rs429608

Variant names:

• chr6-31962685-G-A
• rs429608
• NM_006929.5:c.1212-29G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 150 publications found

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 Gene-Disease associations (from GenCC):

• trichohepatoenteric syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• trichohepatoenteric syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SKIC2	NM_006929.5	c.1212-29G>A		intron_variant	Intron 11 of 27	ENST00000375394.7	NP_008860.4
SKIC2	XM_011514815.4	c.1212-29G>A		intron_variant	Intron 11 of 24		XP_011513117.1
SKIC2	XM_047419259.1	c.1212-29G>A		intron_variant	Intron 11 of 24		XP_047275215.1
SKIC2	XM_047419260.1	c.1212-29G>A		intron_variant	Intron 11 of 23		XP_047275216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIC2	ENST00000375394.7	c.1212-29G>A		intron_variant	Intron 11 of 27	1	NM_006929.5	ENSP00000364543.2

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

GnomAD2 exomes AF: 0.143 AC: 35468 AN: 248358 AF XY: 0.148

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 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

African (AFR) AF: 0.214 AC: 7146 AN: 33342

American (AMR) AF: 0.103 AC: 4625 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 2482 AN: 26092

East Asian (EAS) AF: 0.0949 AC: 3765 AN: 39668

South Asian (SAS) AF: 0.210 AC: 18048 AN: 86122

European-Finnish (FIN) AF: 0.120 AC: 6330 AN: 52646

Middle Eastern (MID) AF: 0.101 AC: 582 AN: 5756

European-Non Finnish (NFE) AF: 0.153 AC: 169780 AN: 1106810

Other (OTH) AF: 0.162 AC: 9772 AN: 60210

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

African (AFR) AF: 0.217 AC: 8975 AN: 41422

American (AMR) AF: 0.133 AC: 2038 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3468

East Asian (EAS) AF: 0.0839 AC: 433 AN: 5160

South Asian (SAS) AF: 0.195 AC: 941 AN: 4814

European-Finnish (FIN) AF: 0.113 AC: 1196 AN: 10580

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.149 AC: 10132 AN: 67986

Other (OTH) AF: 0.166 AC: 350 AN: 2114

Alfa AF: 0.146 Hom.: 7608

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

-

Department of Ophthalmology and Visual Sciences Kyoto University

Significance: not provided

Review Status: no classification provided

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs429608; hg19: chr6-31930462;