Variant 20-31373069-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_054112.3(DEFB118):c.271A>G(p.Thr91Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DEFB118
NM_054112.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.33

Variant links:

Genes affected

DEFB118 (HGNC:16196): (defensin beta 118) This gene encodes a member of the beta subfamily of defensins. Beta-defensins are antimicrobial peptides that protect tissues and organs from infection by a variety of microorganisms. Expression of this gene is regulated by androgen, and the encoded protein binds to sperm and exhibits antibacterial activity against E. coli. This gene is found in a cluster with other beta-defensin genes on the long arm of chromosome 20. [provided by RefSeq, Nov 2014]

DEFB118 links:

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=0.12493563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB118	NM_054112.3 linkuse as main transcript	c.271A>G	p.Thr91Ala	missense_variant	2/2	ENST00000253381.3	NP_473453.1	Q96PH6A0A384MTK2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB118	ENST00000253381.3 linkuse as main transcript	c.271A>G	p.Thr91Ala	missense_variant	2/2	1	NM_054112.3	ENSP00000253381.2		Q96PH6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251348

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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.:

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 submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.271A>G (p.T91A) alteration is located in exon 2 (coding exon 2) of the DEFB118 gene. This alteration results from a A to G substitution at nucleotide position 271, causing the threonine (T) at amino acid position 91 to be replaced by an alanine (A). 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

0.081

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.5

DANN

Benign

0.97

DEOGEN2

Benign

0.024

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.33

M_CAP

Benign

0.0038

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

REVEL

Benign

0.052

Sift

Benign

0.076

Sift4G

Uncertain

0.019

Polyphen

0.94

Vest4

0.028

MutPred

0.27

Gain of sheet (P = 0.0221);

MVP

0.076

MPC

0.12

ClinPred

0.30

GERP RS

-0.25

Varity_R

0.066

gMVP

0.22

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over