6-38288300-C-T

Position:

• chr6-38288300-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001099272.2(BTBD9):​c.1426G>A​(p.Ala476Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTBD9 NM_001099272.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD9	NM_001099272.2	c.1426G>A	p.Ala476Thr	missense_variant	8/11	ENST00000481247.6	NP_001092742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD9	ENST00000481247.6	c.1426G>A	p.Ala476Thr	missense_variant	8/11	5	NM_001099272.2	ENSP00000418751	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.1426G>A (p.A476T) alteration is located in exon 9 (coding exon 7) of the BTBD9 gene. This alteration results from a G to A substitution at nucleotide position 1426, causing the alanine (A) at amino acid position 476 to be replaced by a threonine (T). 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	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	.;D;D;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;.;D;D
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.5	.;M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.5	N;N;.;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.026	D;D;.;D
Sift4G	Uncertain	0.025	D;D;.;D
Polyphen		1.0	.;D;D;.
Vest4		0.89
MutPred		0.43		.;Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;
MVP		0.92
MPC		1.1
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.24
gMVP		0.38

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.

Other links and lift over

hg19: chr6-38256076;