20-31308549-T-A

Variant names:

• chr20-31308549-T-A
• NM_001037731.1:c.37A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037731.1(DEFB116):​c.37A>T​(p.Ile13Phe) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEFB116 NM_001037731.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.607
• Publications: 0 publications found

Genes affected

DEFB116 (HGNC:18097): (defensin beta 116) Defensins form a family of antimicrobial and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18653104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037731.1. 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
	DEFB116	NM_001037731.1	MANE Select	c.37A>T	p.Ile13Phe	missense	Exon 1 of 2	NP_001032820.1	Q30KQ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB116	ENST00000400549.1	TSL:1 MANE Select	c.37A>T	p.Ile13Phe	missense	Exon 1 of 2	ENSP00000383396.1	Q30KQ4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Benign	0.19
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.61
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.010
Sift	Benign	0.10	T
Sift4G	Benign	0.13	T
Polyphen		0.044	B
Vest4		0.43
MutPred		0.32		Gain of catalytic residue at I13 (P = 0.1276)
MVP		0.16
MPC		0.00094
ClinPred		0.097	T
GERP RS		1.9
PromoterAI		-0.021	Neutral
Varity_R		0.12
gMVP		0.26
Mutation Taster		=83/17	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

hg19: chr20-29896352;