NM_139074.4:c.91G>C

Variant names:

• chr20-158815-G-C
• rs12624954
• NM_139074.4:c.91G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_139074.4(DEFB127):​c.91G>C​(p.Gly31Arg) 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. 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. G31A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEFB127 NM_139074.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25
• Publications: 32 publications found

Genes affected

DEFB127 (HGNC:16206): (defensin beta 127) 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139074.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB127	NM_139074.4	MANE Select	c.91G>C	p.Gly31Arg	missense	Exon 2 of 2	NP_620713.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB127	ENST00000382388.4	TSL:1 MANE Select	c.91G>C	p.Gly31Arg	missense	Exon 2 of 2	ENSP00000371825.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.12
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	-0.085	T
PhyloP100		3.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Benign	0.18
Sift	Benign	0.043	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.13		Gain of solvent accessibility (P = 0.0037)
MVP		0.53
MPC		0.24
ClinPred		0.86	D
GERP RS		3.1
Varity_R		0.54
gMVP		0.71
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: 11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12624954; hg19: chr20-139456;