Variant chr1-92102555-C-A 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.430C>A(p.Gln144Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,443,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

BTBD8
NM_001376131.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.138

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=0.07730469).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD8	NM_001376131.1 linkuse as main transcript	c.430C>A	p.Gln144Lys	missense_variant	3/18	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.430C>A	p.Gln144Lys	missense_variant	3/18	5	NM_001376131.1	ENSP00000490161.1	Q5XKL5-3
BTBD8	ENST00000342818.4 linkuse as main transcript	c.430C>A	p.Gln144Lys	missense_variant	3/9	1		ENSP00000343686.3	A0A8V8N7F1
BTBD8	ENST00000370382.7 linkuse as main transcript	n.697C>A		non_coding_transcript_exon_variant	3/6	1
BTBD8	ENST00000635934.1 linkuse as main transcript	n.430C>A		non_coding_transcript_exon_variant	3/17	5		ENSP00000490386.1	B4DKD6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

241922

Hom.:

AF XY:

0.00000764

AC XY:

AN XY:

130958

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1443672

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717924

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:

0.00000453

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Dec 20, 2023

The c.430C>A (p.Q144K) alteration is located in exon 3 (coding exon 3) of the BTBD8 gene. This alteration results from a C to A substitution at nucleotide position 430, causing the glutamine (Q) at amino acid position 144 to be replaced by a lysine (K). 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

0.069

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.7

DANN

Benign

0.43

DEOGEN2

Benign

0.0059

.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

.;M

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.52

.;N

REVEL

Benign

0.028

Sift

Benign

0.20

.;T

Sift4G

Benign

0.24

.;T

Polyphen

0.10

.;B

Vest4

0.16

MutPred

0.45

Gain of methylation at Q144 (P = 0.0191);Gain of methylation at Q144 (P = 0.0191);

MVP

0.73

MPC

0.34

ClinPred

0.046

GERP RS

2.1

Varity_R

0.060

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

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