rs2731826

chr5-95554420-G-Achr5-95554420-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014639.4(SKIC3):c.-228+516C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,022 control chromosomes in the GnomAD database, including 2,172 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 0.16 (2172 hom., cov: 32)
• Consequence: SKIC3 NM_014639.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538

Genes affected

SKIC3 (HGNC:23639): (SKI3 subunit of superkiller complex) This gene encodes a protein with twenty tetratricopeptide (TPR) repeats. Tetratricopeptide repeat containing motifs are found in a variety of proteins and may mediate protein-protein interactions and chaperone activity. Mutations in this gene are associated with trichohepatoenteric syndrome. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKIC3	NM_014639.4	c.-228+516C>T		intron_variant		ENST00000358746.7
SKIC3	XM_047417937.1	c.-1641C>T		5_prime_UTR_variant	1/43
SKIC3	XM_047417938.1	c.-228+516C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC3	ENST00000358746.7	c.-228+516C>T		intron_variant		1	NM_014639.4	P4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24578 AN: 151904 Hom.: 2168 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.162 AC: 24611 AN: 152022 Hom.: 2172 Cov.: 32 AF XY: 0.163 AC XY: 12095 AN XY: 74306

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.158

Alfa AF: 0.138 Hom.: 1549

Bravo AF: 0.164

Asia WGS AF: 0.252 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.2
Dann	Benign	0.72

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: rs2731826; hg19: chr5-94890124;