Variant 8-11994068-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001302695.2(DEFB134):c.113G>T(p.Cys38Phe) 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 1,461,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DEFB134
NM_001302695.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

DEFB134 (HGNC:32399): (defensin beta 134) 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]

DEFB134 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB134	NM_001302695.2 linkuse as main transcript	c.113G>T	p.Cys38Phe	missense_variant	3/3	ENST00000382205.6	NP_001289624.1	Q4QY38
DEFB134	XM_017013724.1 linkuse as main transcript	c.113G>T	p.Cys38Phe	missense_variant	3/3		XP_016869213.1	Q4QY38
DEFB134	XM_047422075.1 linkuse as main transcript	c.113G>T	p.Cys38Phe	missense_variant	2/2		XP_047278031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB134	ENST00000382205.6 linkuse as main transcript	c.113G>T	p.Cys38Phe	missense_variant	3/3	1	NM_001302695.2	ENSP00000371640.4		Q4QY38
DEFB134	ENST00000526438.6 linkuse as main transcript	c.113G>T	p.Cys38Phe	missense_variant	2/2	1		ENSP00000435010.1		Q4QY38

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250916

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

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:

1461418

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

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

May 25, 2022

The c.113G>T (p.C38F) alteration is located in exon 2 (coding exon 2) of the DEFB134 gene. This alteration results from a G to T substitution at nucleotide position 113, causing the cysteine (C) at amino acid position 38 to be replaced by a phenylalanine (F). 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

0.89

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.48

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.18

T;T

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.57

M_CAP

Benign

0.027

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Pathogenic

0.89

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-11

D;.

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.70

MutPred

0.23

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.91

MPC

0.00060

ClinPred

1.0

GERP RS

3.6

Varity_R

0.94

gMVP

0.81

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