GeneBe

rs1180861221

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024649.5(BBS1):​c.729C>A​(p.Ser243Arg) 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 (★). Synonymous variant affecting the same amino acid position (i.e. S243S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

BBS1
NM_024649.5 missense

Scores

6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.370

Publications

0 publications found
Variant links:
Genes affected
BBS1 (HGNC:966): (Bardet-Biedl syndrome 1) Mutations in this gene have been observed in patients with the major form (type 1) of Bardet-Biedl syndrome. The encoded protein may play a role in eye, limb, cardiac and reproductive system development. [provided by RefSeq, Jul 2008]
ZDHHC24 (HGNC:27387): (zinc finger DHHC-type containing 24) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Predicted to be involved in peptidyl-L-cysteine S-palmitoylation and protein targeting to membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1724751).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024649.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
BBS1
NM_024649.5
MANE Select
c.729C>Ap.Ser243Arg
missense
Exon 9 of 17NP_078925.3
ZDHHC24
NM_001348571.2
c.*213G>T
3_prime_UTR
Exon 5 of 5NP_001335500.1E9PLR9

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
BBS1
ENST00000318312.12
TSL:1 MANE Select
c.729C>Ap.Ser243Arg
missense
Exon 9 of 17ENSP00000317469.7Q8NFJ9-1
ENSG00000256349
ENST00000419755.3
TSL:2
c.840C>Ap.Ser280Arg
missense
Exon 9 of 17ENSP00000398526.3
ZDHHC24
ENST00000526986.5
TSL:1
c.*213G>T
3_prime_UTR
Exon 5 of 5ENSP00000431321.1E9PLR9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Bardet-Biedl syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Uncertain
0.021
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
6.6
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.47
T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.29
N
LIST_S2
Uncertain
0.89
D
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.34
T
MutationAssessor
Benign
1.3
L
PhyloP100
-0.37
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.1
N
REVEL
Uncertain
0.41
Sift
Benign
0.44
T
Sift4G
Benign
0.58
T
Polyphen
0.66
P
Vest4
0.55
MutPred
0.34
Gain of methylation at S243 (P = 0.0441)
MVP
0.73
MPC
0.26
ClinPred
0.34
T
GERP RS
0.21
Varity_R
0.056
gMVP
0.39
Mutation Taster
=76/24
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1180861221; hg19: chr11-66288746; API