NM_054112.3:c.53T>C

Variant names:

• chr20-31368703-T-C
• NM_054112.3:c.53T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_054112.3(DEFB118):​c.53T>C​(p.Ile18Thr) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DEFB118 NM_054112.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.728
• Publications: 0 publications found

Genes affected

DEFB118 (HGNC:16196): (defensin beta 118) This gene encodes a member of the beta subfamily of defensins. Beta-defensins are antimicrobial peptides that protect tissues and organs from infection by a variety of microorganisms. Expression of this gene is regulated by androgen, and the encoded protein binds to sperm and exhibits antibacterial activity against E. coli. This gene is found in a cluster with other beta-defensin genes on the long arm of chromosome 20. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036166936).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054112.3. 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
	DEFB118	NM_054112.3	MANE Select	c.53T>C	p.Ile18Thr	missense	Exon 1 of 2	NP_473453.1	Q96PH6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB118	ENST00000253381.3	TSL:1 MANE Select	c.53T>C	p.Ile18Thr	missense	Exon 1 of 2	ENSP00000253381.2	Q96PH6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.020	N
PhyloP100		-0.73
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.020
Sift	Benign	0.48	T
Sift4G	Benign	0.99	T
Polyphen		0.26	B
Vest4		0.27
MutPred		0.29		Gain of phosphorylation at I18 (P = 0.0637)
MVP		0.014
MPC		0.10
ClinPred		0.081	T
GERP RS		-5.9
PromoterAI		-0.017	Neutral
Varity_R		0.037
gMVP		0.47
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr20-29956506;