rs976529

Positions:

chr1-243308160-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_006642.5(SDCCAG8):c.912C>T(p.Thr304Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,614,026 control chromosomes in the GnomAD database, including 693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 49 hom., cov: 33)

Exomes 𝑓: 0.028 ( 644 hom. )

Consequence

SDCCAG8
NM_006642.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.48

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:

SDCCAG8 (HGNC:):

SDCCAG8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 1-243308160-C-T is Benign according to our data. Variant chr1-243308160-C-T is described in ClinVar as [Benign]. Clinvar id is 260013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-243308160-C-T is described in Lovd as [Benign]. Variant chr1-243308160-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.48 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0206 (3134/152268) while in subpopulation NFE AF= 0.0315 (2145/68022). AF 95% confidence interval is 0.0304. There are 49 homozygotes in gnomad4. There are 1449 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDCCAG8	NM_006642.5 linkuse as main transcript	c.912C>T	p.Thr304Thr	synonymous_variant	8/18	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SDCCAG8	ENST00000366541.8 linkuse as main transcript	c.912C>T	p.Thr304Thr	synonymous_variant	8/18	1	NM_006642.5	ENSP00000355499.3	Q86SQ7-1
SDCCAG8	ENST00000435549.1 linkuse as main transcript	c.252C>T	p.Thr84Thr	synonymous_variant	3/11	1		ENSP00000410200.1	A0A0C4DG71
SDCCAG8	ENST00000463012.1 linkuse as main transcript	n.272C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

3135

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00495

Gnomad AMI

AF:

0.0692

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0315

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0201

AC:

5064

AN:

251390

Hom.:

AF XY:

0.0205

AC XY:

2785

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00541

Gnomad AMR exome

AF:

0.0160

Gnomad ASJ exome

AF:

0.00962

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00536

Gnomad FIN exome

AF:

0.0154

Gnomad NFE exome

AF:

0.0324

Gnomad OTH exome

AF:

0.0240

GnomAD4 exome

AF:

0.0275

AC:

40206

AN:

1461758

Hom.:

644

Cov.:

AF XY:

0.0270

AC XY:

19602

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00469

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.00980

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00664

Gnomad4 FIN exome

AF:

0.0189

Gnomad4 NFE exome

AF:

0.0323

Gnomad4 OTH exome

AF:

0.0238

GnomAD4 genome

AF:

0.0206

AC:

3134

AN:

152268

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

1449

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00491

Gnomad4 AMR

AF:

0.0284

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.0315

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0268

Hom.:

Bravo

AF:

0.0217

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0293

EpiControl

AF:

0.0321

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Senior-Loken syndrome 7

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Bardet-Biedl syndrome 16

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Kidney disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 01, 2018

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.3

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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