4-122743101-G-T

Variant names:

• chr4-122743101-G-T
• NM_152618.3:c.1209G>T
• BBS12 p.Val403Val

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152618.3(BBS12):​c.1209G>T​(p.Val403Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V403V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BBS12 NM_152618.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.831 with no splicing effect.

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.1209G>T	p.Val403Val	synonymous	Exon 2 of 2	NP_689831.2
	BBS12	NM_001178007.2		c.1209G>T	p.Val403Val	synonymous	Exon 3 of 3	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.1209G>T	p.Val403Val	synonymous	Exon 2 of 2	ENSP00000319062.3	Q6ZW61
	BBS12	ENST00000542236.5	TSL:2	c.1209G>T	p.Val403Val	synonymous	Exon 3 of 3	ENSP00000438273.1	Q6ZW61

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 68

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.059
DANN	Benign	0.49
PhyloP100		-0.83

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

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

Other links and lift over

hg19: chr4-123664256;