5-95464530-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014639.4(SKIC3):c.*77G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,135,074 control chromosomes in the GnomAD database, including 8,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2515 hom., cov: 32)
  • Exomes 𝑓: 0.10 (6286 hom.)
• Consequence: SKIC3 NM_014639.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.14

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 5-95464530-C-T is Benign according to our data. Variant chr5-95464530-C-T is described in ClinVar as [Benign]. Clinvar id is 1283989.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKIC3	NM_014639.4	c.*77G>A		3_prime_UTR_variant	43/43	ENST00000358746.7
SKIC3	XM_047417937.1	c.*77G>A		3_prime_UTR_variant	43/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC3	ENST00000358746.7	c.*77G>A		3_prime_UTR_variant	43/43	1	NM_014639.4	P4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23492 AN: 151776 Hom.: 2509 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.00926

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.104 AC: 101946 AN: 983182 Hom.: 6286 Cov.: 13 AF XY: 0.104 AC XY: 52190 AN XY: 503342

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.0772

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.00382

Gnomad4 SAS exome AF: 0.0968

Gnomad4 FIN exome AF: 0.0731

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.155 AC: 23502 AN: 151892 Hom.: 2515 Cov.: 32 AF XY: 0.152 AC XY: 11292 AN XY: 74226

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.00928

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.0723

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.151

Alfa AF: 0.129 Hom.: 394

Bravo AF: 0.163

Asia WGS AF: 0.0580 AC: 203 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	13
Dann	Benign	0.61

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: rs7534; hg19: chr5-94800234;