rs193920885

chr5-95543278-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014639.4(SKIC3):c.140G>C(p.Gly47Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. G47G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SKIC3 NM_014639.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.52

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKIC3	NM_014639.4	c.140G>C	p.Gly47Ala	missense_variant	5/43	ENST00000358746.7
SKIC3	XM_047417937.1	c.140G>C	p.Gly47Ala	missense_variant	5/43
SKIC3	XM_047417938.1	c.140G>C	p.Gly47Ala	missense_variant	5/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKIC3	ENST00000358746.7	c.140G>C	p.Gly47Ala	missense_variant	5/43	1	NM_014639.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Uncertain	-0.038	T
MutationAssessor	Uncertain	2.1	M;M;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.88	D
Polyphen		1.0	D;D;.
Vest4		0.93
MutPred		0.85		Gain of MoRF binding (P = 0.1826);Gain of MoRF binding (P = 0.1826);Gain of MoRF binding (P = 0.1826);
MVP		0.82
MPC		0.45
ClinPred		0.99	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs193920885; hg19: chr5-94878982; COSMIC: COSV62456677; COSMIC: COSV62456677;