rs406936

Variant names:

• chr6-31965384-G-A
• rs406936
• NM_006929.5:c.1972-399G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31965384-G-A
• chr6-31965384-G-C
• chr6-31965384-G-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.1972-399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,916 control chromosomes in the GnomAD database, including 3,477 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 (3477 hom., cov: 32)
• Consequence: SKIC2 NM_006929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 39 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=-0.86).
• 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 rank	MANE	Protein	UniProt
SKIC2	NM_006929.5	c.1972-399G>A		intron_variant	Intron 17 of 27	ENST00000375394.7	NP_008860.4
SKIC2	XM_011514815.4	c.1972-399G>A		intron_variant	Intron 17 of 24		XP_011513117.1
SKIC2	XM_047419259.1	c.1972-399G>A		intron_variant	Intron 17 of 24		XP_047275215.1
SKIC2	XM_047419260.1	c.1972-399G>A		intron_variant	Intron 17 of 23		XP_047275216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIC2	ENST00000375394.7	c.1972-399G>A		intron_variant	Intron 17 of 27	1	NM_006929.5	ENSP00000364543.2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28572 AN: 151798 Hom.: 3471 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0982

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.188 AC: 28610 AN: 151916 Hom.: 3477 Cov.: 32 AF XY: 0.186 AC XY: 13796 AN XY: 74238

African (AFR) AF: 0.341 AC: 14102 AN: 41364

American (AMR) AF: 0.183 AC: 2795 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3472

East Asian (EAS) AF: 0.0982 AC: 508 AN: 5172

South Asian (SAS) AF: 0.201 AC: 965 AN: 4802

European-Finnish (FIN) AF: 0.0672 AC: 709 AN: 10544

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

European-Non Finnish (NFE) AF: 0.127 AC: 8634 AN: 67972

Other (OTH) AF: 0.207 AC: 438 AN: 2114

Alfa AF: 0.145 Hom.: 6306

Bravo AF: 0.204

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.5
DANN	Benign	0.42
PhyloP100		2.7
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: rs406936; hg19: chr6-31933161;