1-243256233-T-TCTC

Position:

• chr1-243256233-T-TCTC

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_006642.5(SDCCAG8):​c.62_64dupTCC​(p.Leu21dup) variant causes a disruptive inframe insertion, splice region 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R22R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SDCCAG8 NM_006642.5 disruptive_inframe_insertion, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_006642.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDCCAG8	NM_006642.5	c.62_64dupTCC	p.Leu21dup	disruptive_inframe_insertion, splice_region_variant	1/18	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.62_64dupTCC	p.Leu21dup	disruptive_inframe_insertion, splice_region_variant	1/18	1	NM_006642.5	ENSP00000355499.3
SDCCAG8	ENST00000490065.5	n.202_204dupTCC		splice_region_variant, non_coding_transcript_exon_variant	1/5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Senior-Loken syndrome 7;C3889474:Bardet-Biedl syndrome 16 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 18, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.62_64dup, results in the insertion of 1 amino acid(s) of the SDCCAG8 protein (p.Leu21dup), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-243419535;