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GeneBe

11-27658395-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM2_SupportingBP4_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 Genomes project. In-silico tool predicts a benign outcome for this variant. 13/20 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

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2283507).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDNFNM_001709.5 linkuse as main transcriptc.170C>A p.Thr57Lys missense_variant 2/2 ENST00000356660.9
BDNF-ASNR_033312.1 linkuse as main transcriptn.460G>T non_coding_transcript_exon_variant 4/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BDNFENST00000356660.9 linkuse as main transcriptc.170C>A p.Thr57Lys missense_variant 2/21 NM_001709.5 P4P23560-1
BDNF-ASENST00000651238.1 linkuse as main transcriptn.534G>T non_coding_transcript_exon_variant 5/8

Frequencies

GnomAD3 genomes
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 submitterclinical testingAmbry GeneticsFeb 10, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.000064
T
BayesDel_noAF
Benign
-0.24
Cadd
Benign
18
Dann
Benign
0.91
DEOGEN2
Benign
0.32
T;T;.;T;T;T;T;T;T;.;T;T;T;T;T;T;.
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.23
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
1.9
L;L;.;L;L;L;L;L;L;.;L;L;L;L;L;L;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Benign
0.39
T
PROVEAN
Benign
0.050
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.20
Sift
Uncertain
0.010
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Benign
0.97
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.012
B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;B
Vest4
0.19
MutPred
0.39
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
0.57
MPC
0.81
ClinPred
0.53
D
GERP RS
6.2
Varity_R
0.060
gMVP
0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-27679942; API