Variant 1-92107884-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001376131.1(BTBD8):c.545A>T(p.Asp182Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000225 in 1,602,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

BTBD8
NM_001376131.1 missense, splice_region

Scores

Splicing: ADA: 0.01120

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

BTBD8 (HGNC:21019): (BTB domain containing 8) Predicted to be involved in clathrin-dependent synaptic vesicle endocytosis; neuron projection development; and synaptic vesicle budding from endosome. Located in nucleoplasm. Colocalizes with AP-2 adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

BTBD8 links:

BTBD8 (HGNC:):

BTBD8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.077227145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD8	NM_001376131.1 linkuse as main transcript	c.545A>T	p.Asp182Val	missense_variant, splice_region_variant	4/18	ENST00000636805.2	NP_001363060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BTBD8	ENST00000636805.2 linkuse as main transcript	c.545A>T	p.Asp182Val	missense_variant, splice_region_variant	4/18	5	NM_001376131.1	ENSP00000490161.1	Q5XKL5-3
BTBD8	ENST00000342818.4 linkuse as main transcript	c.545A>T	p.Asp182Val	missense_variant, splice_region_variant	4/9	1		ENSP00000343686.3	A0A8V8N7F1
BTBD8	ENST00000370382.7 linkuse as main transcript	n.812A>T		splice_region_variant, non_coding_transcript_exon_variant	4/6	1
BTBD8	ENST00000635934.1 linkuse as main transcript	n.545A>T		splice_region_variant, non_coding_transcript_exon_variant	4/17	5		ENSP00000490386.1	B4DKD6

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000332

AC:

AN:

240714

Hom.:

AF XY:

0.00000767

AC XY:

AN XY:

130348

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.0000959

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000228

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1449978

Hom.:

Cov.:

AF XY:

0.00000693

AC XY:

AN XY:

721230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000969

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000250

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000384

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

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 submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.545A>T (p.D182V) alteration is located in exon 4 (coding exon 4) of the BTBD8 gene. This alteration results from a A to T substitution at nucleotide position 545, causing the aspartic acid (D) at amino acid position 182 to be replaced by a valine (V). 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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.017

Sift

Benign

0.049

.;D

Sift4G

Benign

0.20

.;T

Polyphen

0.0020

.;B

Vest4

0.38

MutPred

0.43

Loss of disorder (P = 0.0196);Loss of disorder (P = 0.0196);

MVP

0.85

MPC

0.30

ClinPred

0.027

GERP RS

2.9

Varity_R

0.095

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.011

dbscSNV1_RF

Benign

0.18

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over