5-95506915-G-C

Variant names:

• chr5-95506915-G-C
• rs144081410
• NM_014639.4:c.3092+19C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

SKIC3 Gene-Disease associations (from GenCC):

• trichohepatoenteric syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
• trichohepatoenteric syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014639.4. 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
	SKIC3	NM_014639.4	MANE Select	c.3092+19C>G		intron	N/A	NP_055454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKIC3	ENST00000358746.7	TSL:1 MANE Select	c.3092+19C>G		intron	N/A	ENSP00000351596.3
	SKIC3	ENST00000698479.1		c.3092+19C>G		intron	N/A	ENSP00000513748.1
	SKIC3	ENST00000649566.1		c.3092+19C>G		intron	N/A	ENSP00000497948.1

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

GnomAD2 exomes AF: 0.00344 AC: 861 AN: 250598 AF XY: 0.00266

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 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

African (AFR) AF: 0.0374 AC: 1249 AN: 33434

American (AMR) AF: 0.00456 AC: 204 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86206

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52870

Middle Eastern (MID) AF: 0.00486 AC: 28 AN: 5762

European-Non Finnish (NFE) AF: 0.000272 AC: 302 AN: 1110546

Other (OTH) AF: 0.00325 AC: 196 AN: 60318

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

African (AFR) AF: 0.0418 AC: 1731 AN: 41448

American (AMR) AF: 0.00459 AC: 70 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10510

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 67952

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

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

Aug 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.33
PhyloP100		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs144081410; hg19: chr5-94842619;