8-7489514-G-T

Position:

• chr8-7489514-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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

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]

ACMG classification

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
DEFB105B	NM_001040703.3	c.200G>T	p.Cys67Phe	missense_variant	3/3	ENST00000335510.7	NP_001035793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB105B	ENST00000335510.7	c.200G>T	p.Cys67Phe	missense_variant	3/3	1	NM_001040703.3	ENSP00000335281.6

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

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 31, 2023

The 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;