15-83066907-G-A

Variant summary

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

The NM_025238.4(BTBD1):c.245C>T(p.Ala82Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000526 in 1,521,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

BTBD1
NM_025238.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Variant links:

Genes affected

BTBD1 (HGNC:1120): (BTB domain containing 1) The C-terminus of the protein encoded by this gene binds topoisomerase I. The N-terminus contains a proline-rich region and a BTB/POZ domain (broad-complex, Tramtrack and bric a brac/Pox virus and Zinc finger), both of which are typically involved in protein-protein interactions. Subcellularly, the protein localizes to cytoplasmic bodies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

BTBD1 links:

(HGNC:):

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=0.10903984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BTBD1	NM_025238.4 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant	1/8	ENST00000261721.9
BTBD1	NM_001011885.2 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant	1/7
BTBD1	XR_007064459.1 linkuse as main transcript	n.346C>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTBD1	ENST00000261721.9 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant	1/8	1	NM_025238.4	P1	Q9H0C5-1
	ENST00000566841.1 linkuse as main transcript	n.735-36517G>A		intron_variant, non_coding_transcript_variant		5
	ENST00000568441.1 linkuse as main transcript	n.38-23414G>A		intron_variant, non_coding_transcript_variant		5
BTBD1	ENST00000379403.2 linkuse as main transcript	c.245C>T	p.Ala82Val	missense_variant	1/7	5			Q9H0C5-2

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.0000146

AC:

AN:

137126

Hom.:

AF XY:

0.00

AC XY:

AN XY:

78398

show subpopulations

Gnomad AFR exome

AF:

0.000370

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1369148

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

677706

show subpopulations

Gnomad4 AFR exome

AF:

0.0000359

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ExAC

AF:

0.00000868

AC:

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

Apr 13, 2022

The c.245C>T (p.A82V) alteration is located in exon 1 (coding exon 1) of the BTBD1 gene. This alteration results from a C to T substitution at nucleotide position 245, causing the alanine (A) at amino acid position 82 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

0.11

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Benign

0.93

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.71

T;T

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

0.92

N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.078

Sift

Benign

0.49

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.41

B;.

Vest4

0.33

MutPred

0.44

Loss of loop (P = 0.0512);Loss of loop (P = 0.0512);

MVP

0.69

MPC

0.77

ClinPred

0.044

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.081

gMVP

0.28

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