5-95554420-G-A

Variant names:

• chr5-95554420-G-A
• rs2731826
• NM_014639.4:c.-228+516C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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.

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.-228+516C>T		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.-228+516C>T		intron	N/A	ENSP00000351596.3
	SKIC3	ENST00000514952.5	TSL:1	c.-228+516C>T		intron	N/A	ENSP00000423742.1
	SKIC3	ENST00000698479.1		c.-228+516C>T		intron	N/A	ENSP00000513748.1

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

African (AFR) AF: 0.202 AC: 8356 AN: 41460

American (AMR) AF: 0.161 AC: 2452 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 250 AN: 3460

East Asian (EAS) AF: 0.328 AC: 1693 AN: 5160

South Asian (SAS) AF: 0.153 AC: 740 AN: 4826

European-Finnish (FIN) AF: 0.159 AC: 1683 AN: 10552

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8986 AN: 67974

Other (OTH) AF: 0.158 AC: 333 AN: 2110

Alfa AF: 0.140 Hom.: 2078

Bravo AF: 0.164

Asia WGS AF: 0.252 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.72
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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: rs2731826; hg19: chr5-94890124;