rs440454

Variant names:

• chr6-31959565-A-G
• rs440454
• NM_006929.5:c.126+165A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-31959565-A-G
• chr6-31959565-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006929.5(SKIC2):​c.126+165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 611,354 control chromosomes in the GnomAD database, including 175,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (47012 hom., cov: 32)
  • Exomes 𝑓: 0.74 (128466 hom.)
• Consequence: SKIC2 NM_006929.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.492
• Publications: 43 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, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• trichohepatoenteric syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-31959565-A-G is Benign according to our data. Variant chr6-31959565-A-G is described in ClinVar as Benign. ClinVar VariationId is 1220566.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKIC2	NM_006929.5	MANE Select	c.126+165A>G		intron	N/A	NP_008860.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKIC2	ENST00000375394.7	TSL:1 MANE Select	c.126+165A>G		intron	N/A	ENSP00000364543.2	Q15477
	SKIC2	ENST00000465703.5	TSL:1	n.178+165A>G		intron	N/A
	SKIC2	ENST00000962078.1		c.126+165A>G		intron	N/A	ENSP00000632137.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118619 AN: 152060 Hom.: 46956 Cov.: 32

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.743 AC: 341035 AN: 459176 Hom.: 128466 Cov.: 4 AF XY: 0.753 AC XY: 183053 AN XY: 243254

African (AFR) AF: 0.908 AC: 11540 AN: 12712

American (AMR) AF: 0.748 AC: 13860 AN: 18540

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 11883 AN: 13790

East Asian (EAS) AF: 0.649 AC: 20206 AN: 31114

South Asian (SAS) AF: 0.896 AC: 42057 AN: 46950

European-Finnish (FIN) AF: 0.722 AC: 24004 AN: 33228

Middle Eastern (MID) AF: 0.879 AC: 1716 AN: 1952

European-Non Finnish (NFE) AF: 0.714 AC: 196128 AN: 274662

Other (OTH) AF: 0.749 AC: 19641 AN: 26228

GnomAD4 genome AF: 0.780 AC: 118735 AN: 152178 Hom.: 47012 Cov.: 32 AF XY: 0.783 AC XY: 58232 AN XY: 74404

African (AFR) AF: 0.906 AC: 37631 AN: 41526

American (AMR) AF: 0.746 AC: 11403 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3025 AN: 3470

East Asian (EAS) AF: 0.679 AC: 3510 AN: 5166

South Asian (SAS) AF: 0.887 AC: 4275 AN: 4820

European-Finnish (FIN) AF: 0.741 AC: 7850 AN: 10594

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48274 AN: 67996

Other (OTH) AF: 0.819 AC: 1732 AN: 2114

Alfa AF: 0.737 Hom.: 117635

Bravo AF: 0.787

Asia WGS AF: 0.844 AC: 2933 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.49
PromoterAI		0.080	Neutral
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: rs440454; hg19: chr6-31927342;