NM_021010.3:c.112G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021010.3(DEFA5):​c.112G>T​(p.Asp38Tyr) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D38H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

DEFA5
NM_021010.3 missense

Scores

1
3
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0900
Variant links:
Genes affected
DEFA5 (HGNC:2764): (defensin alpha 5) Defensins are a family of antimicrobial and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. Several of the alpha defensin genes appear to be clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 5, is highly expressed in the secretory granules of Paneth cells of the ileum. [provided by RefSeq, Oct 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33809158).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DEFA5NM_021010.3 linkc.112G>T p.Asp38Tyr missense_variant Exon 1 of 2 ENST00000330590.4 NP_066290.1 Q01523

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DEFA5ENST00000330590.4 linkc.112G>T p.Asp38Tyr missense_variant Exon 1 of 2 1 NM_021010.3 ENSP00000329890.2 Q01523

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.13
T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.0069
N
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.34
T
MetaSVM
Benign
-0.94
T
PrimateAI
Benign
0.41
T
PROVEAN
Pathogenic
-6.3
D
REVEL
Benign
0.054
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.30
MutPred
0.57
Loss of disorder (P = 0.0627);
MVP
0.43
MPC
0.00054
ClinPred
0.86
D
GERP RS
-1.2
Varity_R
0.26
gMVP
0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777619310; hg19: chr8-6914108; API