20-145513-G-T

Variant names:

• chr20-145513-G-T
• rs201416351
• NM_030931.4:c.157G>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.157G>T​(p.Gly53Cys) 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 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DEFB126 NM_030931.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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=0.1620464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB126	NM_030931.4	c.157G>T	p.Gly53Cys	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.157G>T	p.Gly53Cys	missense_variant	Exon 2 of 2	1	NM_030931.4	ENSP00000371835.3
DEFB126	ENST00000542572.1	n.127+25G>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000408 AC: 1 AN: 245394 Hom.: 0 AF XY: 0.00000755 AC XY: 1 AN XY: 132522

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: 0.0000338

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: 1 AN: 1461782 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

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.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.6
DANN	Benign	0.97
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.086
Sift	Uncertain	0.020	D
Sift4G	Benign	0.072	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.31		Gain of methylation at K54 (P = 0.0157);
MVP		0.10
MPC		0.54
ClinPred		0.69	D
GERP RS		-7.3
Varity_R		0.53
gMVP		0.53

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: rs201416351; hg19: chr20-126154;