chr5-95536867-G-C

Variant names:

• chr5-95536867-G-C
• rs767456366
• NM_014639.4:c.701C>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.701C>G​(p.Pro234Arg) 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).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SKIC3 NM_014639.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 8.64

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, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIC3	NM_014639.4	c.701C>G	p.Pro234Arg	missense_variant	Exon 10 of 43	ENST00000358746.7	NP_055454.1
SKIC3	XM_047417937.1	c.701C>G	p.Pro234Arg	missense_variant	Exon 10 of 43		XP_047273893.1
SKIC3	XM_047417938.1	c.701C>G	p.Pro234Arg	missense_variant	Exon 10 of 29		XP_047273894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIC3	ENST00000358746.7	c.701C>G	p.Pro234Arg	missense_variant	Exon 10 of 43	1	NM_014639.4	ENSP00000351596.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Sep 16, 2018

Gharavi Laboratory, Columbia University

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	.;T;T
M_CAP	Uncertain	0.089	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.1	.;D;D
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0040	.;D;D
Sift4G	Uncertain	0.0050	.;D;D
Polyphen		0.99	D;D;D
Vest4		0.83
MutPred		0.66		Gain of MoRF binding (P = 0.0659);Gain of MoRF binding (P = 0.0659);.;
MVP		0.93
MPC		0.34
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs767456366; hg19: chr5-94872571;