1-243415810-G-C

Variant summary

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

The NM_006642.5(SDCCAG8):c.1725G>C(p.Glu575Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E575E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SDCCAG8 NM_006642.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDCCAG8	NM_006642.5	c.1725G>C	p.Glu575Asp	missense_variant	14/18	ENST00000366541.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.1725G>C	p.Glu575Asp	missense_variant	14/18	1	NM_006642.5	P1
SDCCAG8	ENST00000435549.1	c.957-10617G>C		intron_variant		1
SDCCAG8	ENST00000493334.1	n.692G>C		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.011	P;P;P
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.24
Sift	Benign	0.27	T
Sift4G	Uncertain	0.040	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.058		Loss of methylation at K570 (P = 0.1325);
MVP		0.59
MPC		0.25
ClinPred		0.92	D
GERP RS		1.6
Varity_R		0.12
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: rs10927011; hg19: chr1-243579112;