Variant 6-38594028-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_001099272.2(BTBD9):c.485G>T(p.Cys162Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,790 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: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

BTBD9
NM_001099272.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.89

Variant links:

Genes affected

BTBD9 (HGNC:21228): (BTB domain containing 9) This locus encodes a BTB/POZ domain-containing protein. This domain is known to be involved in protein-protein interactions. Polymorphisms at this locus have been reported to be associated with susceptibility to Restless Legs Syndrome and may also be associated with Tourette Syndrome. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2011]

BTBD9 links:

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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=0.25462115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTBD9	NM_001099272.2 linkuse as main transcript	c.485G>T	p.Cys162Phe	missense_variant	3/11	ENST00000481247.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTBD9	ENST00000481247.6 linkuse as main transcript	c.485G>T	p.Cys162Phe	missense_variant	3/11	5	NM_001099272.2	P1	Q96Q07-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249458

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

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:

0.00000274

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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, 2023

The c.485G>T (p.C162F) alteration is located in exon 4 (coding exon 2) of the BTBD9 gene. This alteration results from a G to T substitution at nucleotide position 485, causing the cysteine (C) at amino acid position 162 to be replaced by a phenylalanine (F). 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

0.28

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Uncertain

-0.050

Cadd

Benign

Dann

Benign

0.95

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;.;D;D;D;D;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.25

T;T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.4

N;N;.;N;.;N;N

REVEL

Benign

0.28

Sift

Benign

0.63

T;T;.;T;.;T;T

Sift4G

Benign

0.65

T;T;.;T;T;T;T

Polyphen

0.88

.;P;P;.;.;.;.

Vest4

0.81

MutPred

0.50

.;Loss of catalytic residue at M160 (P = 0.0799);Loss of catalytic residue at M160 (P = 0.0799);.;.;Loss of catalytic residue at M160 (P = 0.0799);.;

MVP

0.78

MPC

0.51

ClinPred

0.38

GERP RS

5.7

Varity_R

0.40

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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