chr4-122742247-GGC-TCA

Variant names:

• chr4-122742247-GGC-TCA
• NM_152618.3:c.355_357delGGCinsTCA
• BBS12 p.Gly119Ser

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM5

The NM_152618.3(BBS12):​c.355_357delGGCinsTCA​(p.Gly119Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G119D) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BBS12 NM_152618.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.11
• Publications: 0 publications found

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]

BBS12 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 12

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Myriad Women's Health, G2P
• BBS12-related ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr4-122742248-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1373840.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152618.3. 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
	BBS12	NM_152618.3	MANE Select	c.355_357delGGCinsTCA	p.Gly119Ser	missense	N/A	NP_689831.2
	BBS12	NM_001178007.2		c.355_357delGGCinsTCA	p.Gly119Ser	missense	N/A	NP_001171478.1	Q6ZW61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS12	ENST00000314218.8	TSL:1 MANE Select	c.355_357delGGCinsTCA	p.Gly119Ser	missense	N/A	ENSP00000319062.3	Q6ZW61
	BBS12	ENST00000542236.5	TSL:2	c.355_357delGGCinsTCA	p.Gly119Ser	missense	N/A	ENSP00000438273.1	Q6ZW61
	BBS12	ENST00000433287.1	TSL:2	c.355_357delGGCinsTCA	p.Gly119Ser	missense	N/A	ENSP00000398912.1	C9J8H7

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-123663402;