5-95506915-G-C

Position:

• chr5-95506915-G-C

Variant summary

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

The NM_014639.4(SKIC3):​c.3092+19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,611,510 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (34 hom.)
• Consequence: SKIC3 NM_014639.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.206

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-95506915-G-C is Benign according to our data. Variant chr5-95506915-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 445953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1858/151958) while in subpopulation AFR AF= 0.0418 (1731/41448). AF 95% confidence interval is 0.0401. There are 39 homozygotes in gnomad4. There are 892 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKIC3	NM_014639.4	c.3092+19C>G		intron_variant		ENST00000358746.7	NP_055454.1
SKIC3	XM_047417937.1	c.3092+19C>G		intron_variant			XP_047273893.1
SKIC3	XM_047417938.1			downstream_gene_variant			XP_047273894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKIC3	ENST00000358746.7	c.3092+19C>G		intron_variant		1	NM_014639.4	ENSP00000351596	P4

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1847 AN: 151840 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.0416

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00344 AC: 861 AN: 250598 Hom.: 15 AF XY: 0.00266 AC XY: 360 AN XY: 135500

Gnomad AFR exome AF: 0.0386

Gnomad AMR exome AF: 0.00440

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000529

Gnomad OTH exome AF: 0.00246

GnomAD4 exome AF: 0.00137 AC: 1997 AN: 1459552 Hom.: 34 Cov.: 30 AF XY: 0.00123 AC XY: 896 AN XY: 726214

Gnomad4 AFR exome AF: 0.0374

Gnomad4 AMR exome AF: 0.00456

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000272

Gnomad4 OTH exome AF: 0.00325

GnomAD4 genome AF: 0.0122 AC: 1858 AN: 151958 Hom.: 39 Cov.: 32 AF XY: 0.0120 AC XY: 892 AN XY: 74264

Gnomad4 AFR AF: 0.0418

Gnomad4 AMR AF: 0.00459

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00652 Hom.: 2

Bravo AF: 0.0141

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 24, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs144081410; hg19: chr5-94842619;