chr1-243256198-ACCCTG-CCCTT

Variant names:

• chr1-243256198-ACCCTG-CCCTT
• NM_006642.5:c.25_30delACCCTGinsCCCTT

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_006642.5(SDCCAG8):​c.25_30delACCCTGinsCCCTT​(p.Thr9ProfsTer24) variant causes a frameshift, missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SDCCAG8 NM_006642.5 frameshift, missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.38
• Publications: 0 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: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 60 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-243256198-ACCCTG-CCCTT is Pathogenic according to our data. Variant chr1-243256198-ACCCTG-CCCTT is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3582346.Status of the report is criteria_provided_single_submitter, 1 stars.

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.25_30delACCCTGinsCCCTT	p.Thr9ProfsTer24	frameshift missense	Exon 1 of 18	NP_006633.1	Q86SQ7-1
	SDCCAG8	NM_001350248.2		c.25_30delACCCTGinsCCCTT	p.Thr9ProfsTer24	frameshift missense	Exon 1 of 19	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.-283_-278delACCCTGinsCCCTT		5_prime_UTR	Exon 1 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.25_30delACCCTGinsCCCTT	p.Thr9ProfsTer24	frameshift missense	Exon 1 of 18	ENSP00000355499.3	Q86SQ7-1
	SDCCAG8	ENST00000884080.1		c.25_30delACCCTGinsCCCTT	p.Thr9ProfsTer24	frameshift missense	Exon 1 of 19	ENSP00000554139.1
	SDCCAG8	ENST00000951623.1		c.25_30delACCCTGinsCCCTT	p.Thr9ProfsTer24	frameshift missense	Exon 1 of 18	ENSP00000621682.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Senior-Loken syndrome 7;C3889474:Bardet-Biedl syndrome 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-243419500;