4-9444547-T-G

Position:

• chr4-9444547-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040448.3(DEFB131A):​c.14T>G​(p.Phe5Cys) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DEFB131A NM_001040448.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.881

Genes affected

DEFB131A (HGNC:18108): (defensin beta 131A) 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 4p16. [provided by RefSeq, Nov 2014]

ACMG classification

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=0.26014268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB131A	NM_001040448.3	c.14T>G	p.Phe5Cys	missense_variant	1/2	ENST00000334879.2	NP_001035538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB131A	ENST00000334879.2	c.14T>G	p.Phe5Cys	missense_variant	1/2	1	NM_001040448.3	ENSP00000335538.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.14T>G (p.F5C) alteration is located in exon 1 (coding exon 1) of the DEFB131 gene. This alteration results from a T to G substitution at nucleotide position 14, causing the phenylalanine (F) at amino acid position 5 to be replaced by a cysteine (C). 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	0.12
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	7.8
DANN	Benign	0.64
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0073	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.00077	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.054
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.60
MutPred		0.32		Loss of stability (P = 0.065);
MVP		0.11
MPC		0.00034
ClinPred		0.31	T
GERP RS		-0.14
Varity_R		0.17
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-9446273;