rs976529

Variant names:

• chr1-243308160-C-T
• rs976529
• NM_006642.5:c.912C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 2.48
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 16

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp
• Senior-Loken syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• ciliopathy

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 260013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 49 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006642.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	NM_006642.5	MANE Select	c.912C>T	p.Thr304Thr	synonymous	Exon 8 of 18	NP_006633.1	Q86SQ7-1
	SDCCAG8	NM_001350248.2		c.1008C>T	p.Thr336Thr	synonymous	Exon 9 of 19	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.618C>T	p.Thr206Thr	synonymous	Exon 8 of 18	NP_001337178.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.912C>T	p.Thr304Thr	synonymous	Exon 8 of 18	ENSP00000355499.3	Q86SQ7-1
	SDCCAG8	ENST00000435549.1	TSL:1	c.252C>T	p.Thr84Thr	synonymous	Exon 3 of 11	ENSP00000410200.1	A0A0C4DG71
	SDCCAG8	ENST00000884080.1		c.1008C>T	p.Thr336Thr	synonymous	Exon 9 of 19	ENSP00000554139.1

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3135 AN: 152150 Hom.: 49 Cov.: 33

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

GnomAD2 exomes AF: 0.0201 AC: 5064 AN: 251390 AF XY: 0.0205

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 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.: 33 AF XY: 0.0270 AC XY: 19602 AN XY: 727182

African (AFR) AF: 0.00469 AC: 157 AN: 33480

American (AMR) AF: 0.0175 AC: 782 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 256 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.00664 AC: 573 AN: 86254

European-Finnish (FIN) AF: 0.0189 AC: 1008 AN: 53390

Middle Eastern (MID) AF: 0.0118 AC: 68 AN: 5768

European-Non Finnish (NFE) AF: 0.0323 AC: 35924 AN: 1111932

Other (OTH) AF: 0.0238 AC: 1437 AN: 60394

GnomAD4 genome AF: 0.0206 AC: 3134 AN: 152268 Hom.: 49 Cov.: 33 AF XY: 0.0195 AC XY: 1449 AN XY: 74446

African (AFR) AF: 0.00491 AC: 204 AN: 41566

American (AMR) AF: 0.0284 AC: 435 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4824

European-Finnish (FIN) AF: 0.0137 AC: 145 AN: 10594

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0315 AC: 2145 AN: 68022

Other (OTH) AF: 0.0223 AC: 47 AN: 2110

Alfa AF: 0.0278 Hom.: 131

Bravo AF: 0.0217

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0293

EpiControl AF: 0.0321

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Bardet-Biedl syndrome 16 (2)
-	-	2	Senior-Loken syndrome 7 (2)
-	-	1	Kidney disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Senior-Loken syndrome 7;C3889474:Bardet-Biedl syndrome 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	7.3
DANN	Benign	0.68
PhyloP100		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs976529; hg19: chr1-243471462;