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GeneBe

11-27658199-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM2_Supporting

The NM_001709.5(BDNF):c.366G>T(p.Met122Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M122T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

BDNF
NM_001709.5 missense

Scores

5
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Links

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDNFNM_001709.5 linkuse as main transcriptc.366G>T p.Met122Ile missense_variant 2/2 ENST00000356660.9
BDNF-ASNR_033312.1 linkuse as main transcriptn.306-42C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BDNFENST00000356660.9 linkuse as main transcriptc.366G>T p.Met122Ile missense_variant 2/21 NM_001709.5 P4P23560-1
BDNF-ASENST00000651238.1 linkuse as main transcriptn.380-42C>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeJun 01, 2022This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 122 of the BDNF protein (p.Met122Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BDNF-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.93
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
Cadd
Uncertain
23
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.60
D;D;.;D;D;D;D;D;D;.;D;D;D;D;D;D;.
Eigen
Uncertain
0.68
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.062
D
MetaRNN
Uncertain
0.46
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.44
T
MutationAssessor
Benign
0.69
N;N;.;N;N;N;N;N;N;.;N;N;N;N;N;N;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.9
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Uncertain
0.32
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.013
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
0.53
P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P
Vest4
0.63
MutPred
0.51
Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);.;Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);.;Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);Loss of disorder (P = 0.0481);.;
MVP
0.80
MPC
1.3
ClinPred
0.79
D
GERP RS
6.1
Varity_R
0.76
gMVP
0.58

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: chr11-27679746; API