6-38175109-C-A

Position:

• chr6-38175109-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099272.2(BTBD9):​c.1715G>T​(p.Gly572Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BTBD9 NM_001099272.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1063149).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD9	NM_001099272.2	c.1715G>T	p.Gly572Val	missense_variant	11/11	ENST00000481247.6	NP_001092742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD9	ENST00000481247.6	c.1715G>T	p.Gly572Val	missense_variant	11/11	5	NM_001099272.2	ENSP00000418751.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Jul 14, 2024

The c.1715G>T (p.G572V) alteration is located in exon 12 (coding exon 10) of the BTBD9 gene. This alteration results from a G to T substitution at nucleotide position 1715, causing the glycine (G) at amino acid position 572 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	0.068
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	.;T;T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.78	T;.;T;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N;N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.37	N;N;.;N
REVEL	Benign	0.092
Sift	Benign	0.12	T;T;.;D
Sift4G	Benign	0.23	T;T;.;T
Polyphen		0.036	.;B;B;.
Vest4		0.087
MutPred		0.11		.;Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);.;
MVP		0.76
MPC		1.2
ClinPred		0.40	T
GERP RS		4.4
Varity_R		0.086
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-38142885;