15-78292621-C-T

Variant names:

• chr15-78292621-C-T
• NM_025234.3:c.314G>A

Variant summary

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

The NM_025234.3(SKIC8):​c.314G>A​(p.Gly105Glu) variant causes a missense change. 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SKIC8 NM_025234.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

Genes affected

SKIC8 (HGNC:30300): (SKI8 subunit of superkiller complex) WDR61 is a subunit of the human PAF and SKI complexes, which function in transcriptional regulation and are involved in events downstream of RNA synthesis, such as RNA surveillance (Zhu et al., 2005 [PubMed 16024656]).[supplied by OMIM, Mar 2008]

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, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIC8	NM_025234.3	c.314G>A	p.Gly105Glu	missense_variant	Exon 5 of 11	ENST00000267973.7	NP_079510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIC8	ENST00000267973.7	c.314G>A	p.Gly105Glu	missense_variant	Exon 5 of 11	1	NM_025234.3	ENSP00000267973.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.314G>A (p.G105E) alteration is located in exon 5 (coding exon 4) of the WDR61 gene. This alteration results from a G to A substitution at nucleotide position 314, causing the glycine (G) at amino acid position 105 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.4	L;L;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-4.9	D;D;D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.029	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.76
MutPred		0.69		Loss of catalytic residue at A104 (P = 0.0889);Loss of catalytic residue at A104 (P = 0.0889);Loss of catalytic residue at A104 (P = 0.0889);
MVP		0.91
MPC		1.3
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.88
gMVP		0.71

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: chr15-78584963;