rs1553941373

chr4-122742929-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152618.3(BBS12):c.1037T>C(p.Ile346Thr) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I346F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BBS12 NM_152618.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34003264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS12	NM_152618.3	c.1037T>C	p.Ile346Thr	missense_variant	2/2	ENST00000314218.8
BBS12	NM_001178007.2	c.1037T>C	p.Ile346Thr	missense_variant	3/3
BBS12	XM_011531680.3	c.1037T>C	p.Ile346Thr	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS12	ENST00000314218.8	c.1037T>C	p.Ile346Thr	missense_variant	2/2	1	NM_152618.3	P1
BBS12	ENST00000542236.5	c.1037T>C	p.Ile346Thr	missense_variant	3/3	2		P1

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

Bardet-Biedl syndrome 12 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Counsyl

Nov 22, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	-0.028
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.47	T;.
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.53
Sift	Benign	0.077	T;T
Sift4G	Uncertain	0.056	T;T
Polyphen		0.97	D;D
Vest4		0.13
MutPred		0.71		Gain of disorder (P = 0.0171);Gain of disorder (P = 0.0171);
MVP		0.87
MPC		0.45
ClinPred		0.81	D
GERP RS		5.7
Varity_R		0.085
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1553941373; hg19: chr4-123664084;