rs587777801

Positions:

• chr4-122742226-ATAG-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The ENST00000314218.8(BBS12):​c.337_339del​(p.Val113del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BBS12 ENST00000314218.8 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.63

Genes affected

BBS12 (HGNC:26648): (Bardet-Biedl syndrome 12) The protein encoded by this gene is part of a complex that is involved in membrane trafficking. The encoded protein is a molecular chaperone that aids in protein folding upon ATP hydrolysis. This protein also plays a role in adipocyte differentiation. Defects in this gene are a cause of Bardet-Biedl syndrome type 12. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000314218.8. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 4-122742226-ATAG-A is Pathogenic according to our data. Variant chr4-122742226-ATAG-A is described in ClinVar as [Pathogenic]. Clinvar id is 1148.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS12	NM_152618.3	c.337_339del	p.Val113del	inframe_deletion	2/2	ENST00000314218.8	NP_689831.2
BBS12	NM_001178007.2	c.337_339del	p.Val113del	inframe_deletion	3/3		NP_001171478.1
BBS12	XM_011531680.3	c.337_339del	p.Val113del	inframe_deletion	2/2		XP_011529982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS12	ENST00000314218.8	c.337_339del	p.Val113del	inframe_deletion	2/2	1	NM_152618.3	ENSP00000319062	P1
BBS12	ENST00000433287.1	c.337_339del	p.Val113del	inframe_deletion	3/3	2		ENSP00000398912
BBS12	ENST00000542236.5	c.337_339del	p.Val113del	inframe_deletion	3/3	2		ENSP00000438273	P1

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Bardet-Biedl syndrome 12 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs587777801; hg19: chr4-123663381;