NM_001040448.3:c.52C>A

Variant names:

• chr4-9444585-C-A
• rs758097415
• NM_001040448.3:c.52C>A

Variant summary

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

The NM_001040448.3(DEFB131A):​c.52C>A​(p.Pro18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. P18L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DEFB131A NM_001040448.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 0 publications found

Genes affected

DEFB131A (HGNC:18108): (defensin beta 131A) 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 4p16. [provided by RefSeq, Nov 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=0.16451392).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040448.3. 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
	DEFB131A	NM_001040448.3	MANE Select	c.52C>A	p.Pro18Thr	missense	Exon 1 of 2	NP_001035538.2	P59861

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB131A	ENST00000334879.2	TSL:1 MANE Select	c.52C>A	p.Pro18Thr	missense	Exon 1 of 2	ENSP00000335538.1	P59861

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458924 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725786

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111522

Other (OTH) AF: 0.00 AC: 0 AN: 60170

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.00070	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.026
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.039
Sift	Benign	0.14	T
Sift4G	Benign	0.57	T
Polyphen		0.90	P
Vest4		0.40
MutPred		0.45		Loss of loop (P = 0.0203)
MVP		0.014
MPC		0.00036
ClinPred		0.21	T
GERP RS		0.31
PromoterAI		-0.019	Neutral
Varity_R		0.076
gMVP		0.087
Mutation Taster		=98/2	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: rs758097415; hg19: chr4-9446311;