8-7016687-G-T

Variant summary

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

The NM_005217.4(DEFA3):​c.164C>A​(p.Pro55Gln) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 27)
Exomes 𝑓: 0.0000023 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DEFA3
NM_005217.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.83
Variant links:
Genes affected
DEFA3 (HGNC:2762): (defensin alpha 3) 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. The protein encoded by this gene, defensin, alpha 3, is found in the microbicidal granules of neutrophils and likely plays a role in phagocyte-mediated host defense. Several alpha defensin genes are clustered on chromosome 8. This gene differs from defensin, alpha 1 by only one amino acid. This gene and the gene encoding defensin, alpha 1 are both subject to copy number variation. [provided by RefSeq, Oct 2014]

Genome browser will be placed here

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=0.13891056).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DEFA3NM_005217.4 linkc.164C>A p.Pro55Gln missense_variant 2/3 ENST00000327857.7 NP_005208.1 P59666Q6EZE9
DEFA3XM_011534741.3 linkc.185C>A p.Pro62Gln missense_variant 3/4 XP_011533043.1
LOC124901875XR_007060790.1 linkn.215G>T non_coding_transcript_exon_variant 2/2
LOC124901875XR_007060791.1 linkn.368G>T non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DEFA3ENST00000327857.7 linkc.164C>A p.Pro55Gln missense_variant 2/31 NM_005217.4 ENSP00000328359.2 P59666

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD3 exomes
AF:
0.0000125
AC:
1
AN:
80058
Hom.:
0
AF XY:
0.0000242
AC XY:
1
AN XY:
41254
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000100
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000235
AC:
3
AN:
1278826
Hom.:
0
Cov.:
27
AF XY:
0.00000315
AC XY:
2
AN XY:
634540
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000951
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
27

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 GeneticsJul 14, 2021The c.164C>A (p.P55Q) alteration is located in exon 2 (coding exon 1) of the DEFA3 gene. This alteration results from a C to A substitution at nucleotide position 164, causing the proline (P) at amino acid position 55 to be replaced by a glutamine (Q). 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
0.088
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
6.1
DANN
Benign
0.96
DEOGEN2
Benign
0.014
T
Eigen
Benign
-0.83
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.00055
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.00096
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.97
T
PrimateAI
Benign
0.32
T
PROVEAN
Benign
0.15
N
REVEL
Benign
0.073
Sift
Uncertain
0.018
D
Sift4G
Benign
0.14
T
Polyphen
0.99
D
Vest4
0.14
MutPred
0.34
Loss of glycosylation at P55 (P = 0.035);
MVP
0.21
MPC
1.9
ClinPred
0.27
T
GERP RS
-3.7
Varity_R
0.025
gMVP
0.072

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: rs1390030049; hg19: chr8-6874209; API