8-11973983-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001033018.2(DEFB136):​c.191T>G​(p.Met64Arg) 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. 14/19 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

DEFB136
NM_001033018.2 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0540
Variant links:
Genes affected
DEFB136 (HGNC:34433): (defensin beta 136) Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The antimicrobial protein encoded by this gene is secreted and is a member of the beta defensin protein family. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 8p23. [provided by RefSeq, Nov 2014]

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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=0.08178404).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DEFB136NM_001033018.2 linkc.191T>G p.Met64Arg missense_variant 2/2 ENST00000382209.2 NP_001028190.2 Q30KP8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DEFB136ENST00000382209.2 linkc.191T>G p.Met64Arg missense_variant 2/21 NM_001033018.2 ENSP00000371644.2 Q30KP8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 08, 2023The c.191T>G (p.M64R) alteration is located in exon 2 (coding exon 2) of the DEFB136 gene. This alteration results from a T to G substitution at nucleotide position 191, causing the methionine (M) at amino acid position 64 to be replaced by an arginine (R). 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
0.24
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
1.3
DANN
Benign
0.23
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.94
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.025
N
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.082
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.037
Sift
Benign
0.52
T
Sift4G
Benign
0.076
T
Polyphen
0.22
B
Vest4
0.35
MutPred
0.26
Loss of helix (P = 0.0376);
MVP
0.014
MPC
0.15
ClinPred
0.16
T
GERP RS
-2.3
Varity_R
0.14
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: chr8-11831492; API