chr11-27658395-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001709.5(BDNF):c.170C>A(p.Thr57Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
BDNF
NM_001709.5 missense
NM_001709.5 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 5.84
Genes affected
BDNF (HGNC:1033): (brain derived neurotrophic factor) This gene encodes a member of the nerve growth factor family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protein. Binding of this protein to its cognate receptor promotes neuronal survival in the adult brain. Expression of this gene is reduced in Alzheimer's, Parkinson's, and Huntington's disease patients. This gene may play a role in the regulation of the stress response and in the biology of mood disorders. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2283507).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BDNF | NM_001709.5 | c.170C>A | p.Thr57Lys | missense_variant | 2/2 | ENST00000356660.9 | |
BDNF-AS | NR_033312.1 | n.460G>T | non_coding_transcript_exon_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BDNF | ENST00000356660.9 | c.170C>A | p.Thr57Lys | missense_variant | 2/2 | 1 | NM_001709.5 | P4 | |
BDNF-AS | ENST00000651238.1 | n.534G>T | non_coding_transcript_exon_variant | 5/8 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2022 | The c.170C>A (p.T57K) alteration is located in exon 1 (coding exon 1) of the BDNF gene. This alteration results from a C to A substitution at nucleotide position 170, causing the threonine (T) at amino acid position 57 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.;T;T;T;T;T;T;.;T;T;T;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;L;L;L;L;L;L;.;L;L;L;L;L;L;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;B
Vest4
MutPred
Gain of ubiquitination at T57 (P = 0.0192);Gain of ubiquitination at T57 (P = 0.0192);.;Gain of ubiquitination at T57 (P = 0.0192);Gain of ubiquitination at T57 (P = 0.0192);Gain of ubiquitination at T57 (P = 0.0192);Gain of ubiquitination at T57 (P = 0.0192);Gain of ubiquitination at T57 (P = 0.0192);Gain of ubiquitination at T57 (P = 0.0192);.;Gain of ubiquitination at T57 (P = 0.0192);Gain of ubiquitination at T57 (P = 0.0192);Gain of ubiquitination at T57 (P = 0.0192);Gain of ubiquitination at T57 (P = 0.0192);Gain of ubiquitination at T57 (P = 0.0192);Gain of ubiquitination at T57 (P = 0.0192);.;
MVP
MPC
0.81
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.