chr6-31959283-A-T

Position:

• chr6-31959283-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006929.5(SKIC2):​c.23-14A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000868 in 1,608,454 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00084 (13 hom.)
• Consequence: SKIC2 NM_006929.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.249

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 6-31959283-A-T is Benign according to our data. Variant chr6-31959283-A-T is described in ClinVar as [Benign]. Clinvar id is 907288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00109 (166/151898) while in subpopulation AMR AF= 0.00779 (119/15282). AF 95% confidence interval is 0.00665. There are 2 homozygotes in gnomad4. There are 79 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKIC2	NM_006929.5	c.23-14A>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000375394.7
SKIC2	XM_011514815.4	c.23-14A>T		splice_polypyrimidine_tract_variant, intron_variant
SKIC2	XM_047419259.1	c.23-14A>T		splice_polypyrimidine_tract_variant, intron_variant
SKIC2	XM_047419260.1	c.23-14A>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC2	ENST00000375394.7	c.23-14A>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006929.5	P1

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 167 AN: 151780 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00348

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00303 AC: 756 AN: 249316 Hom.: 7 AF XY: 0.00222 AC XY: 299 AN XY: 134920

Gnomad AFR exome AF: 0.000432

Gnomad AMR exome AF: 0.0205

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00187

Gnomad SAS exome AF: 0.0000656

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00263

GnomAD4 exome AF: 0.000844 AC: 1230 AN: 1456556 Hom.: 13 Cov.: 31 AF XY: 0.000709 AC XY: 513 AN XY: 724018

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.0194

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00712

Gnomad4 SAS exome AF: 0.0000465

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.00135

GnomAD4 genome AF: 0.00109 AC: 166 AN: 151898 Hom.: 2 Cov.: 33 AF XY: 0.00106 AC XY: 79 AN XY: 74236

Gnomad4 AFR AF: 0.000483

Gnomad4 AMR AF: 0.00779

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00349

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000383 Hom.: 0

Bravo AF: 0.00177

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Trichohepatoenteric syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs145129911; hg19: chr6-31927060;