20-188073-C-G

Variant names:

• chr20-188073-C-G
• rs2011113079
• NM_001037732.3:c.95G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001037732.3(DEFB128):​c.95G>C​(p.Cys32Ser) 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 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C32F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DEFB128 NM_001037732.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82
• Publications: 0 publications found

Genes affected

DEFB128 (HGNC:18106): (defensin beta 128) 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. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037732.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB128	NM_001037732.3	MANE Select	c.95G>C	p.Cys32Ser	missense	Exon 2 of 2	NP_001032821.1	Q7Z7B8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB128	ENST00000334391.5	TSL:1 MANE Select	c.95G>C	p.Cys32Ser	missense	Exon 2 of 2	ENSP00000335382.4	Q7Z7B8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461728 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727168

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111922

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Pathogenic	1.1	D
PhyloP100		2.8
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-9.7	D
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.66		Gain of disorder (P = 0.0061)
MVP		0.97
MPC		0.030
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.99
gMVP		0.71
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs2011113079; hg19: chr20-168714;