chr8-11973983-A-G

Variant names:

• chr8-11973983-A-G
• rs1799541675
• NM_001033018.2:c.191T>C

Variant summary

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

The NM_001033018.2(DEFB136):​c.191T>C​(p.Met64Thr) 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. 14/20 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. M64R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEFB136 NM_001033018.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 0 publications found

Genes affected

DEFB136 (HGNC:34433): (defensin beta 136) 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 8p23. [provided by RefSeq, Nov 2014]

ENSG00000290829 (HGNC:):

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=0.08216843).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033018.2. 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
	DEFB136	NM_001033018.2	MANE Select	c.191T>C	p.Met64Thr	missense	Exon 2 of 2	NP_001028190.2	Q30KP8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB136	ENST00000382209.2	TSL:1 MANE Select	c.191T>C	p.Met64Thr	missense	Exon 2 of 2	ENSP00000371644.2	Q30KP8
	ENSG00000290829	ENST00000715791.1		n.491T>C		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000290829	ENST00000715788.1		n.297+40848T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.45
DANN	Benign	0.29
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.054
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.027
Sift	Benign	0.58	T
Sift4G	Benign	0.18	T
Polyphen		0.19	B
Vest4		0.39
MutPred		0.31		Loss of helix (P = 0.0376)
MVP		0.014
MPC		0.11
ClinPred		0.15	T
GERP RS		-2.3
Varity_R		0.052
gMVP		0.28
Mutation Taster		=97/3	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: rs1799541675; hg19: chr8-11831492;