6-31966595-C-T

Variant names:

• chr6-31966595-C-T
• rs454212
• NM_006929.5:c.2203-114C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006929.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKIC2	NM_006929.5	MANE Select	c.2203-114C>T		intron	N/A	NP_008860.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKIC2	ENST00000375394.7	TSL:1 MANE Select	c.2203-114C>T		intron	N/A	ENSP00000364543.2
	SKIC2	ENST00000465703.5	TSL:1	n.2702-114C>T		intron	N/A
	SKIC2	ENST00000962078.1		c.2305-114C>T		intron	N/A	ENSP00000632137.1

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

African (AFR) AF: 0.345 AC: 7827 AN: 22668

American (AMR) AF: 0.128 AC: 4467 AN: 34922

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 1878 AN: 18610

East Asian (EAS) AF: 0.0991 AC: 3655 AN: 36882

South Asian (SAS) AF: 0.222 AC: 14334 AN: 64642

European-Finnish (FIN) AF: 0.0742 AC: 3204 AN: 43156

Middle Eastern (MID) AF: 0.133 AC: 459 AN: 3442

European-Non Finnish (NFE) AF: 0.130 AC: 87412 AN: 673802

Other (OTH) AF: 0.154 AC: 6544 AN: 42372

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

African (AFR) AF: 0.341 AC: 14101 AN: 41380

American (AMR) AF: 0.183 AC: 2801 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 366 AN: 3468

East Asian (EAS) AF: 0.0987 AC: 510 AN: 5168

South Asian (SAS) AF: 0.201 AC: 967 AN: 4812

European-Finnish (FIN) AF: 0.0674 AC: 714 AN: 10596

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8636 AN: 67964

Other (OTH) AF: 0.207 AC: 436 AN: 2108

Alfa AF: 0.141 Hom.: 5505

Bravo AF: 0.204

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.73
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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