Genetic Variant BPTF:p.Pro67Leu (chr17-67825924-C-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_182641.4(BPTF):c.200C>T(p.Pro67Leu) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BPTF
NM_182641.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57

Publications

0 publications found

Variant links:

Genes affected

BPTF (HGNC:3581): (bromodomain PHD finger transcription factor) This gene was identified by the reactivity of its encoded protein to a monoclonal antibody prepared against brain homogenates from patients with Alzheimer's disease. Analysis of the original protein (fetal Alz-50 reactive clone 1, or FAC1), identified as an 810 aa protein containing a DNA-binding domain and a zinc finger motif, suggested it might play a role in the regulation of transcription. High levels of FAC1 were detected in fetal brain and in patients with neurodegenerative diseases. The protein encoded by this gene is actually much larger than originally thought, and it also contains a C-terminal bromodomain characteristic of proteins that regulate transcription during proliferation. The encoded protein is highly similar to the largest subunit of the Drosophila NURF (nucleosome remodeling factor) complex. In Drosophila, the NURF complex, which catalyzes nucleosome sliding on DNA and interacts with sequence-specific transcription factors, is necessary for the chromatin remodeling required for transcription. Two alternative transcripts encoding different isoforms have been described completely. [provided by RefSeq, Jul 2008]

BPTF Gene-Disease associations (from GenCC):

syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Illumina
neurodevelopmental disorder with dysmorphic facies and distal limb anomalies
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

BPTF 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=0.25843942).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BPTF	NM_182641.4	MANE Select	c.200C>T	p.Pro67Leu	missense	Exon 1 of 28	NP_872579.2
BPTF	NM_001439139.1		c.200C>T	p.Pro67Leu	missense	Exon 1 of 29	NP_001426068.1
BPTF	NM_001439140.1		c.200C>T	p.Pro67Leu	missense	Exon 1 of 31	NP_001426069.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BPTF	ENST00000306378.11	TSL:1 MANE Select	c.200C>T	p.Pro67Leu	missense	Exon 1 of 28	ENSP00000307208.6	Q12830-2
BPTF	ENST00000582467.2	TSL:5	c.200C>T	p.Pro67Leu	missense	Exon 1 of 32	ENSP00000463776.2	J3QQK4
BPTF	ENST00000321892.8	TSL:5	c.200C>T	p.Pro67Leu	missense	Exon 1 of 30	ENSP00000315454.4	Q12830-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

867968

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

404242

African (AFR)

AF:

0.00

AC:

AN:

16398

American (AMR)

AF:

0.00

AC:

AN:

2158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5966

East Asian (EAS)

AF:

0.00

AC:

AN:

5422

South Asian (SAS)

AF:

0.00

AC:

AN:

17610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1782

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

785186

Other (OTH)

AF:

0.00

AC:

AN:

29324

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.43

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.55

PhyloP100

2.6

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.094

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.021

Polyphen

0.0060

Vest4

0.14

MutPred

0.16

Loss of loop (P = 0.0288)

MVP

0.51

MPC

1.1

ClinPred

0.19

GERP RS

1.4

PromoterAI

-0.048

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.089

gMVP

0.23

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over