15-83041744-A-C

Variant summary

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

The NM_025238.4(BTBD1):c.846T>G(p.Ile282Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

BTBD1
NM_025238.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.480

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=0.15014836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BTBD1	NM_025238.4 linkuse as main transcript	c.846T>G	p.Ile282Met	missense_variant	4/8	ENST00000261721.9
LOC124903542	XR_007064742.1 linkuse as main transcript	n.1320-19743A>C		intron_variant, non_coding_transcript_variant
BTBD1	NM_001011885.2 linkuse as main transcript	c.846T>G	p.Ile282Met	missense_variant	4/7
BTBD1	XR_007064459.1 linkuse as main transcript	n.947T>G		non_coding_transcript_exon_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTBD1	ENST00000261721.9 linkuse as main transcript	c.846T>G	p.Ile282Met	missense_variant	4/8	1	NM_025238.4	P1	Q9H0C5-1
	ENST00000566841.1 linkuse as main transcript	n.735-61680A>C		intron_variant, non_coding_transcript_variant		5
	ENST00000568441.1 linkuse as main transcript	n.37+19137A>C		intron_variant, non_coding_transcript_variant		5
	ENST00000570202.1 linkuse as main transcript	n.63-19743A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

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:

0.0000358

AC:

AN:

251412

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000489

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:

0.0000109

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

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

Dec 07, 2023

The c.846T>G (p.I282M) alteration is located in exon 4 (coding exon 4) of the BTBD1 gene. This alteration results from a T to G substitution at nucleotide position 846, causing the isoleucine (I) at amino acid position 282 to be replaced by a methionine (M). 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

0.25

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.084

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.13

Sift

Benign

0.081

T;T

Sift4G

Benign

0.091

T;T

Polyphen

0.14

B;.

Vest4

0.42

MutPred

0.49

Gain of disorder (P = 0.0688);Gain of disorder (P = 0.0688);

MVP

0.78

MPC

0.64

ClinPred

0.15

GERP RS

1.9

Varity_R

0.13

gMVP

0.41

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