1-243305133-C-T

Variant names:

• chr1-243305133-C-T
• rs397515337
• NM_006642.5:c.740+356C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 10P and 1B. PM2 PP5_Very_Strong BP4

The NM_001350251.2(SDCCAG8):​c.-416C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000828 in 217,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: SDCCAG8 NM_001350251.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:8
• Conservation: PhyloP100: -0.970
• Publications: 6 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• Senior-Loken syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Bardet-Biedl syndrome

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-243305133-C-T is Pathogenic according to our data. Variant chr1-243305133-C-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 60.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350251.2. 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.740+356C>T		intron	N/A	NP_006633.1	Q86SQ7-1
	SDCCAG8	NM_001350251.2		c.-416C>T		5_prime_UTR_premature_start_codon_gain	Exon 9 of 21	NP_001337180.1
	SDCCAG8	NM_001350251.2		c.-416C>T		5_prime_UTR	Exon 9 of 21	NP_001337180.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.740+356C>T		intron	N/A	ENSP00000355499.3	Q86SQ7-1
	SDCCAG8	ENST00000435549.1	TSL:1	c.80+356C>T		intron	N/A	ENSP00000410200.1	A0A0C4DG71
	SDCCAG8	ENST00000476722.6	TSL:3	c.454C>T	p.Arg152Cys	missense	Exon 5 of 5	ENSP00000473868.1	S4R323

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 151982 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000124 AC: 1 AN: 8058 AF XY: 0.000217

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000300

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000122 AC: 8 AN: 65308 Hom.: 0 Cov.: 0 AF XY: 0.000109 AC XY: 4 AN XY: 36828

African (AFR) AF: 0.00 AC: 0 AN: 624

American (AMR) AF: 0.00 AC: 0 AN: 2482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1368

East Asian (EAS) AF: 0.00 AC: 0 AN: 1554

South Asian (SAS) AF: 0.00 AC: 0 AN: 12658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.000173 AC: 7 AN: 40400

Other (OTH) AF: 0.000320 AC: 1 AN: 3128

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151982 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74232

African (AFR) AF: 0.0000242 AC: 1 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000693 Hom.: 0

Bravo AF: 0.0000718

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic/Likely pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
2	-	-	Bardet-Biedl syndrome 16 (2)
2	-	-	Senior-Loken syndrome 7 (2)
1	-	-	Bardet-Biedl syndrome (1)
1	-	-	not provided (1)
1	-	-	SDCCAG8-related disorder (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	-1.0
CADD	Benign	3.7
DANN	Benign	0.69
PhyloP100		-0.97
Mutation Taster		=32/68	disease causing (ClinVar)

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: rs397515337; hg19: chr1-243468435;