rs869025208

chr7-33146353-GAAATGGACAAGGT-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_Moderate PP5

The NM_198428.3(BBS9):c.104_112+4del variant causes a splice donor, coding sequence change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. G34G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBS9 NM_198428.3 splice_donor, coding_sequence
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.47

Genes affected

BBS9 (HGNC:30000): (Bardet-Biedl syndrome 9) This gene is downregulated by parathyroid hormone in osteoblastic cells, and therefore is thought to be involved in parathyroid hormone action in bones. The exact function of this gene has not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PVS1: Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.045795795 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PP5: Variant 7-33146353-GAAATGGACAAGGT-G is Pathogenic according to our data. Variant chr7-33146353-GAAATGGACAAGGT-G is described in ClinVar as [Pathogenic]. Clinvar id is 217437.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-33146353-GAAATGGACAAGGT-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.104_112+4del		splice_donor_variant, coding_sequence_variant	2/23	ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.104_112+4del		splice_donor_variant, coding_sequence_variant	2/23	1	NM_198428.3	P3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Bardet-Biedl syndrome 9 Pathogenic:1

Pathogenic, no assertion criteria provided

research

Department Of Medical Genetics, Faculty Of Medicine, Ege University

Oct 05, 2015

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs869025208; hg19: chr7-33185965;