rs747363592

Variant names:

• chr1-243256187-C-G
• rs747363592
• NM_006642.5:c.14C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-243256187-C-G
• chr1-243256187-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006642.5(SDCCAG8):​c.14C>G​(p.Pro5Arg) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P5L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SDCCAG8 NM_006642.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.736
• Publications: 0 publications found

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]

SDCCAG8 Gene-Disease associations (from GenCC):

• Senior-Loken syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Bardet-Biedl syndrome 16

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21045908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDCCAG8	NM_006642.5	c.14C>G	p.Pro5Arg	missense_variant	Exon 1 of 18	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.14C>G	p.Pro5Arg	missense_variant	Exon 1 of 18	1	NM_006642.5	ENSP00000355499.3
SDCCAG8	ENST00000490065.5	n.154C>G		non_coding_transcript_exon_variant	Exon 1 of 5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.62	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.74
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.13
Sift	Uncertain	0.014	D
Sift4G	Benign	0.49	T
Polyphen		0.98	D
Vest4		0.39
MutPred		0.27		Loss of glycosylation at P5 (P = 0.0342);
MVP		0.49
MPC		0.28
ClinPred		0.92	D
GERP RS		2.4
PromoterAI		-0.0034	Neutral
Varity_R		0.14
gMVP		0.32
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs747363592; hg19: chr1-243419489;