rs145877279

Variant names:

• chr1-243271036-G-A
• rs145877279
• NM_006642.5:c.279G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-243271036-G-A
• chr1-243271036-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006642.5(SDCCAG8):​c.279G>A​(p.Pro93Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,612,954 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (20 hom.)
• Consequence: SDCCAG8 NM_006642.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.642

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 1-243271036-G-A is Benign according to our data. Variant chr1-243271036-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-243271036-G-A is described in Lovd as [Benign]. Variant chr1-243271036-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.642 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0014 (213/152128) while in subpopulation SAS AF= 0.00828 (40/4830). AF 95% confidence interval is 0.00625. There are 1 homozygotes in gnomad4. There are 106 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDCCAG8	NM_006642.5	c.279G>A	p.Pro93Pro	synonymous_variant	Exon 3 of 18	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.279G>A	p.Pro93Pro	synonymous_variant	Exon 3 of 18	1	NM_006642.5	ENSP00000355499.3
SDCCAG8	ENST00000482234.1	n.12G>A		non_coding_transcript_exon_variant	Exon 1 of 6	3
SDCCAG8	ENST00000490065.5	n.432G>A		non_coding_transcript_exon_variant	Exon 3 of 5	4
SDCCAG8	ENST00000491888.1	n.*4G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 215 AN: 152010 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000984

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00201

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00245 AC: 617 AN: 251360 Hom.: 5 AF XY: 0.00284 AC XY: 386 AN XY: 135846

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.000489

Gnomad SAS exome AF: 0.00875

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.00216

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00214 AC: 3119 AN: 1460826 Hom.: 20 Cov.: 29 AF XY: 0.00235 AC XY: 1709 AN XY: 726792

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.00831

Gnomad4 FIN exome AF: 0.000412

Gnomad4 NFE exome AF: 0.00196

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.00140 AC: 213 AN: 152128 Hom.: 1 Cov.: 31 AF XY: 0.00143 AC XY: 106 AN XY: 74380

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000982

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.00828

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.00201

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00160 Hom.: 0

Bravo AF: 0.00137

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00234

EpiControl AF: 0.00231

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Jan 19, 2017

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SDCCAG8: BP4, BP7, BS2 -

SDCCAG8-related disorder Benign:1

Aug 09, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

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

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bardet-Biedl syndrome 16 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.6
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs145877279; hg19: chr1-243434338; COSMIC: COSV105219472; COSMIC: COSV105219472;