6-31967534-C-T

Variant names:

• chr6-31967534-C-T
• rs453821
• NM_006929.5:c.2583+157C>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.2583+157C>T 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 151,914 control chromosomes in the GnomAD database, including 3,434 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 (3434 hom., cov: 32)
• Consequence: SKIC2 NM_006929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 20 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 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.2583+157C>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.2583+157C>T		intron	N/A	ENSP00000364543.2
	SKIC2	ENST00000465703.5	TSL:1	n.3082+157C>T		intron	N/A
	SKIC2	ENST00000697840.1		c.2619+157C>T		intron	N/A	ENSP00000513458.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28459 AN: 151796 Hom.: 3427 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0982

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.188 AC: 28498 AN: 151914 Hom.: 3434 Cov.: 32 AF XY: 0.185 AC XY: 13747 AN XY: 74274

African (AFR) AF: 0.340 AC: 14026 AN: 41312

American (AMR) AF: 0.182 AC: 2784 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3468

East Asian (EAS) AF: 0.0982 AC: 506 AN: 5152

South Asian (SAS) AF: 0.200 AC: 964 AN: 4814

European-Finnish (FIN) AF: 0.0670 AC: 710 AN: 10604

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.127 AC: 8619 AN: 67974

Other (OTH) AF: 0.205 AC: 432 AN: 2108

Alfa AF: 0.142 Hom.: 1511

Bravo AF: 0.204

Asia WGS AF: 0.223 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs453821; hg19: chr6-31935311; COSMIC: COSV61713439; COSMIC: COSV61713439;