Genetic Variant BDP1:p.Ile121Phe (chr5-71458727-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_018429.3(BDP1):c.361A>T(p.Ile121Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. I121V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BDP1
NM_018429.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

Publications

0 publications found

Variant links:

Genes affected

BDP1 (HGNC:13652): (B double prime 1, subunit of RNA polymerase III transcription initiation factor IIIB) The product of this gene is a subunit of the TFIIIB transcription initiation complex, which recruits RNA polymerase III to target promoters in order to initiate transcription. The encoded protein localizes to concentrated aggregates in the nucleus, and is required for transcription from all three types of polymerase III promoters. It is phosphorylated by casein kinase II during mitosis, resulting in its release from chromatin and suppression of polymerase III transcription. [provided by RefSeq, Jul 2008]

BDP1 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal recessive 112
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia, Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

BDP1 links:

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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=0.09100923).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018429.3. 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
	BDP1	NM_018429.3	MANE Select	c.361A>T	p.Ile121Phe	missense	Exon 2 of 39	NP_060899.2	A6H8Y1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDP1	ENST00000358731.9	TSL:1 MANE Select	c.361A>T	p.Ile121Phe	missense	Exon 2 of 39	ENSP00000351575.4	A6H8Y1-1
	BDP1	ENST00000508917.6	TSL:1	n.553A>T		non_coding_transcript_exon	Exon 2 of 32

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.011

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.67

M_CAP

Benign

0.0052

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

1.6

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.073

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.015

Polyphen

0.0070

Vest4

0.10

MutPred

0.097

Gain of loop (P = 0.1069)

MVP

0.12

MPC

0.055

ClinPred

0.17

GERP RS

4.4

Varity_R

0.18

gMVP

0.063

Mutation Taster

=87/13

polymorphism

(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

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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