Variant chr8-7828916-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_152251.4(DEFB106A):c.161G>A(p.Cys54Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000045 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DEFB106A
NM_152251.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

DEFB106A (HGNC:18088): (defensin beta 106A) Defensins form a family of antimicrobial and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. Chromosome 8p23 contains at least two copies of the duplicated beta-defensin cluster. This duplication results in two identical copies of defensin, beta 106, DEFB106A and DEFB106B, in head-to-head orientation. This gene, DEFB106A, represents the more centromeric copy. [provided by RefSeq, Oct 2014]

DEFB106A links:

LOC124901865 (HGNC:):

LOC124901865 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB106A	NM_152251.4 linkuse as main transcript	c.161G>A	p.Cys54Tyr	missense_variant	2/2	ENST00000335186.3	NP_689464.1	Q8N104
LOC124901865	use as main transcript	n.7828916G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB106A	ENST00000335186.3 linkuse as main transcript	c.161G>A	p.Cys54Tyr	missense_variant	2/2	1	NM_152251.4	ENSP00000335307.2		Q8N104

Frequencies

GnomAD3 genomes

AF:

0.000189

AC:

AN:

143024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000153

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000445

AC:

AN:

1391720

Hom.:

Cov.:

AF XY:

0.0000347

AC XY:

AN XY:

690784

show subpopulations

Gnomad4 AFR exome

AF:

0.00113

Gnomad4 AMR exome

AF:

0.0000467

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000160

Gnomad4 OTH exome

AF:

0.000105

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000196

AC:

AN:

143140

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

AN XY:

69346

show subpopulations

Gnomad4 AFR

AF:

0.000699

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000153

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000337

Hom.:

ExAC

AF:

0.0000843

AC:

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

Aug 28, 2024

The c.161G>A (p.C54Y) alteration is located in exon 2 (coding exon 2) of the DEFB106A gene. This alteration results from a G to A substitution at nucleotide position 161, causing the cysteine (C) at amino acid position 54 to be replaced by a tyrosine (Y). 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

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

0.090

Eigen_PC

Benign

0.067

FATHMM_MKL

Uncertain

0.80

M_CAP

Uncertain

0.098

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.61

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-11

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.88

MVP

0.64

MPC

5.0

ClinPred

0.85

GERP RS

4.1

Varity_R

0.92

gMVP

0.78

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