rs115098969

chr1-243330565-G-Achr1-243330565-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_006642.5(SDCCAG8):c.1094G>A(p.Arg365Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,614,050 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R365T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (3 hom.)
• Consequence: SDCCAG8 NM_006642.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.19

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002281934).
• BP6: Variant 1-243330565-G-A is Benign according to our data. Variant chr1-243330565-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 193691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-243330565-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00208 (316/152204) while in subpopulation AFR AF= 0.0073 (303/41506). AF 95% confidence interval is 0.00662. There are 1 homozygotes in gnomad4. There are 151 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDCCAG8	NM_006642.5	c.1094G>A	p.Arg365Lys	missense_variant	10/18	ENST00000366541.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.1094G>A	p.Arg365Lys	missense_variant	10/18	1	NM_006642.5	P1
SDCCAG8	ENST00000435549.1	c.434G>A	p.Arg145Lys	missense_variant	5/11	1

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 314 AN: 152086 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00727

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000525 AC: 132 AN: 251400 Hom.: 0 AF XY: 0.000420 AC XY: 57 AN XY: 135872

Gnomad AFR exome AF: 0.00702

Gnomad AMR exome AF: 0.000463

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: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000168 AC: 245 AN: 1461846 Hom.: 3 Cov.: 31 AF XY: 0.000129 AC XY: 94 AN XY: 727216

Gnomad4 AFR exome AF: 0.00591

Gnomad4 AMR exome AF: 0.000425

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.000315

GnomAD4 genome AF: 0.00208 AC: 316 AN: 152204 Hom.: 1 Cov.: 32 AF XY: 0.00203 AC XY: 151 AN XY: 74416

Gnomad4 AFR AF: 0.00730

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000396 Hom.: 0

Bravo AF: 0.00222

ESP6500AA AF: 0.00749 AC: 33

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000642 AC: 78

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 30, 2016	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 05, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 20, 2021	- -

SDCCAG8-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Senior-Loken syndrome 7;C3889474:Bardet-Biedl syndrome 16 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	9.3
Dann	Benign	0.72
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.096	N
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.0023	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.5	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.82	N;N
REVEL	Benign	0.026
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;.
Vest4		0.075
MVP		0.20
MPC		0.040
ClinPred		0.0010	T
GERP RS		2.0
Varity_R		0.045
gMVP		0.039

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: rs115098969; hg19: chr1-243493867;