Variant chr15-83066917-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_025238.4(BTBD1):c.235C>A(p.Arg79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

BTBD1
NM_025238.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

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:

BTBD1 (HGNC:):

BTBD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a modified_residue Omega-N-methylarginine (size 0) in uniprot entity BTBD1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16197392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD1	NM_025238.4 linkuse as main transcript	c.235C>A	p.Arg79Ser	missense_variant	1/8	ENST00000261721.9	NP_079514.1	Q9H0C5-1A0A024R224
BTBD1	NM_001011885.2 linkuse as main transcript	c.235C>A	p.Arg79Ser	missense_variant	1/7		NP_001011885.1	Q9H0C5-2
BTBD1	XR_007064459.1 linkuse as main transcript	n.336C>A		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BTBD1	ENST00000261721.9 linkuse as main transcript	c.235C>A	p.Arg79Ser	missense_variant	1/8	1	NM_025238.4	ENSP00000261721.4	Q9H0C5-1
BTBD1	ENST00000379403.2 linkuse as main transcript	c.235C>A	p.Arg79Ser	missense_variant	1/7	5		ENSP00000368713.2	Q9H0C5-2
ENSG00000259805	ENST00000566841.1 linkuse as main transcript	n.735-36507G>T		intron_variant		5
ENSG00000260351	ENST00000568441.1 linkuse as main transcript	n.38-23404G>T		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.23e-7

AC:

AN:

1382702

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685644

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:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 24, 2024

The c.235C>A (p.R79S) alteration is located in exon 1 (coding exon 1) of the BTBD1 gene. This alteration results from a C to A substitution at nucleotide position 235, causing the arginine (R) at amino acid position 79 to be replaced by a serine (S). 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

0.17

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.65

T;T

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.24

Sift

Benign

0.46

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.0060

B;.

Vest4

0.12

MutPred

0.42

Loss of methylation at R79 (P = 0.0069);Loss of methylation at R79 (P = 0.0069);

MVP

0.78

MPC

0.67

ClinPred

0.41

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.25

gMVP

0.48

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over