1-243256183-T-C

Position:

• chr1-243256183-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_006642.5(SDCCAG8):​c.10T>C​(p.Ser4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SDCCAG8 NM_006642.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.773

Genes affected

SDCCAG8 (HGNC:10671): (SHH signaling and ciliogenesis regulator SDCCAG8) This gene encodes a centrosome associated protein. This protein may be involved in organizing the centrosome during interphase and mitosis. Mutations in this gene are associated with retinal-renal ciliopathy. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity SDCG8_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2399582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDCCAG8	NM_006642.5	c.10T>C	p.Ser4Pro	missense_variant	1/18	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.10T>C	p.Ser4Pro	missense_variant	1/18	1	NM_006642.5	ENSP00000355499	P1
SDCCAG8	ENST00000490065.5	n.150T>C		non_coding_transcript_exon_variant	1/5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

SDCCAG8-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 31, 2024

The SDCCAG8 c.10T>C variant is predicted to result in the amino acid substitution p.Ser4Pro. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.50	N
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.14
Sift	Uncertain	0.014	D
Sift4G	Benign	0.26	T
Polyphen		0.99	D
Vest4		0.25
MutPred		0.22		Gain of catalytic residue at S4 (P = 0.0044);
MVP		0.61
MPC		0.30
ClinPred		0.91	D
GERP RS		1.8
Varity_R		0.35
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs1271164856; hg19: chr1-243419485;