8-7489514-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001040703.3(DEFB105B):​c.200G>T​(p.Cys67Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

DEFB105B
NM_001040703.3 missense

Scores

4
5
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58
Variant links:
Genes affected
DEFB105B (HGNC:29930): (defensin beta 105B) 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. Chromosome 8p23 contains at least two copies of the duplicated beta-defensin cluster. This duplication results in two identical copies of defensin, beta 105, DEFB105A and DEFB105B, in tail-to-tail orientation. This gene, DEFB105B, represents the more telomeric copy. [provided by RefSeq, Oct 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DEFB105BNM_001040703.3 linkc.200G>T p.Cys67Phe missense_variant 3/3 ENST00000335510.7 NP_001035793.1 Q8NG35A0A0K0K1I4B2RU30

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DEFB105BENST00000335510.7 linkc.200G>T p.Cys67Phe missense_variant 3/31 NM_001040703.3 ENSP00000335281.6 Q8NG35

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.0000252
AC:
2
AN:
79374
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
44796
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000441
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 31, 2023The c.200G>T (p.C67F) alteration is located in exon 3 (coding exon 3) of the DEFB105B gene. This alteration results from a G to T substitution at nucleotide position 200, causing the cysteine (C) at amino acid position 67 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Benign
22
DANN
Uncertain
0.97
Eigen
Benign
0.031
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.21
N
M_CAP
Benign
0.045
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Uncertain
0.077
D
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-10
D
REVEL
Uncertain
0.50
Sift
Benign
0.034
D
Sift4G
Pathogenic
0.0
D
Vest4
0.77
MutPred
0.52
Gain of catalytic residue at C67 (P = 0.0621);
MVP
0.91
ClinPred
1.0
D
GERP RS
2.2
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-7347036; API