1-243256195-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006642.5(SDCCAG8):ā€‹c.22T>Cā€‹(p.Ser8Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

SDCCAG8
NM_006642.5 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.25
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10250935).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SDCCAG8NM_006642.5 linkc.22T>C p.Ser8Pro missense_variant 1/18 ENST00000366541.8 NP_006633.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SDCCAG8ENST00000366541.8 linkc.22T>C p.Ser8Pro missense_variant 1/181 NM_006642.5 ENSP00000355499.3 Q86SQ7-1
SDCCAG8ENST00000490065.5 linkn.162T>C non_coding_transcript_exon_variant 1/54

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251470
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461862
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Senior-Loken syndrome 7;C3889474:Bardet-Biedl syndrome 16 Uncertain:2
Uncertain significance, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsSep 20, 2021- -
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 13, 2022This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1470091). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 8 of the SDCCAG8 protein (p.Ser8Pro). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.067
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.087
FATHMM_MKL
Benign
0.54
D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.75
N
REVEL
Benign
0.070
Sift
Uncertain
0.012
D
Sift4G
Benign
0.082
T
Polyphen
0.0040
B
Vest4
0.33
MutPred
0.26
Loss of phosphorylation at S8 (P = 0.0309);
MVP
0.45
MPC
0.15
ClinPred
0.89
D
GERP RS
3.1
Varity_R
0.42
gMVP
0.27

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1193390013; hg19: chr1-243419497; API