rs148818431

Variant names:

• chr1-243271024-T-C
• rs148818431
• NM_006642.5:c.267T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_006642.5(SDCCAG8):​c.267T>C​(p.Ser89Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000943 in 1,613,524 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00097 (2 hom.)
• Consequence: SDCCAG8 NM_006642.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:2
• Conservation: PhyloP100: 1.60
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-243271024-T-C is Benign according to our data. Variant chr1-243271024-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 167663.
• BP7: Synonymous conserved (PhyloP=1.6 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000651 (99/152122) while in subpopulation NFE AF = 0.000985 (67/68016). AF 95% confidence interval is 0.000795. There are 0 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.267T>C	p.Ser89Ser	synonymous	Exon 3 of 18	NP_006633.1	Q86SQ7-1
	SDCCAG8	NM_001350248.2		c.267T>C	p.Ser89Ser	synonymous	Exon 3 of 19	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.-28T>C		5_prime_UTR	Exon 3 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.267T>C	p.Ser89Ser	synonymous	Exon 3 of 18	ENSP00000355499.3	Q86SQ7-1
	SDCCAG8	ENST00000884080.1		c.267T>C	p.Ser89Ser	synonymous	Exon 3 of 19	ENSP00000554139.1
	SDCCAG8	ENST00000951623.1		c.267T>C	p.Ser89Ser	synonymous	Exon 3 of 18	ENSP00000621682.1

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 99 AN: 152122 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000823 AC: 207 AN: 251390 AF XY: 0.000817

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00111

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000974 AC: 1423 AN: 1461402 Hom.: 2 Cov.: 29 AF XY: 0.000946 AC XY: 688 AN XY: 727038

African (AFR) AF: 0.0000896 AC: 3 AN: 33466

American (AMR) AF: 0.000827 AC: 37 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00387 AC: 101 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53414

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.00111 AC: 1234 AN: 1111676

Other (OTH) AF: 0.000729 AC: 44 AN: 60372

GnomAD4 genome AF: 0.000651 AC: 99 AN: 152122 Hom.: 0 Cov.: 31 AF XY: 0.000498 AC XY: 37 AN XY: 74312

African (AFR) AF: 0.000314 AC: 13 AN: 41450

American (AMR) AF: 0.000262 AC: 4 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000985 AC: 67 AN: 68016

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.00109 Hom.: 0

Bravo AF: 0.000752

EpiCase AF: 0.000981

EpiControl AF: 0.00166

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Bardet-Biedl syndrome 16 (1)
-	1	-	not provided (1)
-	-	1	not specified (1)
-	1	-	Senior-Loken syndrome 7 (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	-0.46
CADD	Benign	9.7
DANN	Benign	0.79
PhyloP100		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs148818431; hg19: chr1-243434326;