2-169493760-T-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP2PP3

The NM_152384.3(BBS5):c.542T>A(p.Phe181Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F181S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BBS5
NM_152384.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.01

Publications

0 publications found

Variant links:

Genes affected

BBS5 (HGNC:970): (Bardet-Biedl syndrome 5) This gene encodes a protein that has been directly linked to Bardet-Biedl syndrome. The primary features of this syndrome include retinal dystrophy, obesity, polydactyly, renal abnormalities and learning disabilities. Experimentation in non-human eukaryotes suggests that this gene is expressed in ciliated cells and that it is required for the formation of cilia. Alternate transcriptional splice variants have been observed but have not been fully characterized. [provided by RefSeq, Jul 2008]

BBS5 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BBS5 links:

ENSG00000251569 (HGNC:):

ENSG00000251569 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 7 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 0.85025 (below the threshold of 3.09). Trascript score misZ: 1.0056 (below the threshold of 3.09). GenCC associations: The gene is linked to Bardet-Biedl syndrome 5, Bardet-Biedl syndrome.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.835

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152384.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS5	NM_152384.3	MANE Select	c.542T>A	p.Phe181Tyr	missense	Exon 7 of 12	NP_689597.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BBS5	ENST00000295240.8	TSL:1 MANE Select	c.542T>A	p.Phe181Tyr	missense	Exon 7 of 12	ENSP00000295240.3
ENSG00000251569	ENST00000513963.1	TSL:2	c.542T>A	p.Phe181Tyr	missense	Exon 7 of 16	ENSP00000424363.1
BBS5	ENST00000392663.6	TSL:1	c.542T>A	p.Phe181Tyr	missense	Exon 7 of 11	ENSP00000376431.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460138

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39606

South Asian (SAS)

AF:

0.00

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110550

Other (OTH)

AF:

0.00

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.16

Eigen

Benign

0.085

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.83

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.44

PhyloP100

8.0

PROVEAN

Benign

-0.80

REVEL

Uncertain

0.34

Sift

Benign

0.22

Sift4G

Benign

0.29

Polyphen

0.0010

Vest4

0.71

MutPred

0.76

Loss of helix (P = 0.1706)

MVP

0.73

MPC

1.1

ClinPred

0.79

GERP RS

6.0

Varity_R

0.26

gMVP

0.41

Mutation Taster

=40/60

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over