rs376573096

Variant names:

• chr20-145658-C-G
• rs376573096
• NM_030931.4:c.302C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-145658-C-G
• chr20-145658-C-T

Variant summary

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

The NM_030931.4(DEFB126):​c.302C>G​(p.Ser101Trp) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEFB126 NM_030931.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.19

Genes affected

DEFB126 (HGNC:15900): (defensin beta 126) 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 20p13. The encoded protein is highly similar to an epididymal-specific secretory protein (ESP13.2) from cynomolgus monkey. Mutation of this gene is associated with impaired sperm function. [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=0.07521185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB126	NM_030931.4	c.302C>G	p.Ser101Trp	missense_variant	Exon 2 of 2	ENST00000382398.4	NP_112193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB126	ENST00000382398.4	c.302C>G	p.Ser101Trp	missense_variant	Exon 2 of 2	1	NM_030931.4	ENSP00000371835.3
DEFB126	ENST00000542572.1	n.207C>G		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.2
DANN	Benign	0.85
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.026
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.018	D
Polyphen		0.0050	B
Vest4		0.26
MutPred		0.20		Loss of glycosylation at S101 (P = 0.0182);
MVP		0.061
MPC		0.14
ClinPred		0.091	T
GERP RS		-1.0
Varity_R		0.057
gMVP		0.19

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

Other links and lift over

dbSNP: rs376573096; hg19: chr20-126299;