rs397514336

Positions:

• chr3-15635515-G-A
• chr3-15635515-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370658.1(BTD):​c.76G>A​(p.Glu26Lys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTD NM_001370658.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

Genes affected

BTD (HGNC:1122): (biotinidase) The protein encoded by this gene functions to recycle protein-bound biotin by cleaving biocytin (biotin-epsilon-lysine), a normal product of carboxylase degradation, resulting in regeneration of free biotin. The encoded protein has also been shown to have biotinyl transferase activity. Mutations in this gene are associated with biotinidase deficiency. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13738978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTD	NM_001370658.1	c.76G>A	p.Glu26Lys	missense_variant	2/4	ENST00000643237.3	NP_001357587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTD	ENST00000643237.3	c.76G>A	p.Glu26Lys	missense_variant	2/4		NM_001370658.1	ENSP00000495254	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	8.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	.;.;T;.;.;.;.;T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.71	.;T;T;.;T;.;T;T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.9	.;.;L;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.8	D;N;.;.;.;.;N;N;N;.
REVEL	Benign	0.26
Sift	Benign	0.12	T;T;.;.;.;.;T;T;T;.
Sift4G	Benign	0.14	T;T;.;.;.;.;T;T;T;.
Polyphen		0.0030	.;.;B;.;.;.;.;.;.;.
Vest4		0.21, 0.21, 0.20
MutPred		0.32		.;.;Gain of ubiquitination at E46 (P = 0.0101);.;Gain of ubiquitination at E46 (P = 0.0101);.;.;.;.;.;
MVP		0.81
MPC		0.079
ClinPred		0.20	T
GERP RS		3.5
Varity_R		0.030
gMVP		0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs397514336; hg19: chr3-15677022;