1-243271036-G-A

Position:

chr1-243271036-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000366541.8(SDCCAG8):c.279G>A(p.Pro93=) 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
ENST00000366541.8 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.642

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]

SDCCAG8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
SDCCAG8	NM_006642.5 linkuse as main transcript	c.279G>A	p.Pro93=	synonymous_variant	3/18	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8 linkuse as main transcript	c.279G>A	p.Pro93=	synonymous_variant	3/18	1	NM_006642.5	ENSP00000355499	P1	Q86SQ7-1
SDCCAG8	ENST00000482234.1 linkuse as main transcript	n.12G>A		non_coding_transcript_exon_variant	1/6	3
SDCCAG8	ENST00000490065.5 linkuse as main transcript	n.432G>A		non_coding_transcript_exon_variant	3/5	4
SDCCAG8	ENST00000491888.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

215

AN:

152010

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00284

AC XY:

386

AN XY:

135846

show subpopulations

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.:

Cov.:

AF XY:

0.00235

AC XY:

1709

AN XY:

726792

show subpopulations

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.:

Cov.:

AF XY:

0.00143

AC XY:

106

AN XY:

74380

show subpopulations

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.:

Bravo

AF:

0.00137

Asia WGS

AF:

0.00318

AC:

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

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jan 19, 2017	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	SDCCAG8: BP4, BP7, BS2 -

SDCCAG8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 09, 2021

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

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Bardet-Biedl syndrome 16

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over