rs534237033

Variant names:

• chr5-95512589-C-A
• NM_014639.4:c.2808G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-95512589-C-A
• chr5-95512589-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014639.4(SKIC3):​c.2808G>T​(p.Trp936Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SKIC3 NM_014639.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.52

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIC3	NM_014639.4	c.2808G>T	p.Trp936Cys	missense_variant	Exon 28 of 43	ENST00000358746.7	NP_055454.1
SKIC3	XM_047417937.1	c.2808G>T	p.Trp936Cys	missense_variant	Exon 28 of 43		XP_047273893.1
SKIC3	XM_047417938.1	c.2778+982G>T		intron_variant	Intron 27 of 28		XP_047273894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIC3	ENST00000358746.7	c.2808G>T	p.Trp936Cys	missense_variant	Exon 28 of 43	1	NM_014639.4	ENSP00000351596.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461700 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-8.5	.;D
REVEL	Uncertain	0.47
Sift	Benign	0.066	.;T
Sift4G	Benign	0.084	.;T
Polyphen		0.93	P;P
Vest4		0.98
MutPred		0.56		Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);
MVP		0.72
MPC		0.25
ClinPred		1.0	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-94848293;