6-38175152-C-T

Variant names:

• chr6-38175152-C-T
• NM_001099272.2:c.1672G>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.1672G>A​(p.Glu558Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BTBD9 NM_001099272.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79

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]

LOC124901315 (HGNC:):

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=0.20927334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD9	NM_001099272.2	c.1672G>A	p.Glu558Lys	missense_variant	Exon 11 of 11	ENST00000481247.6	NP_001092742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD9	ENST00000481247.6	c.1672G>A	p.Glu558Lys	missense_variant	Exon 11 of 11	5	NM_001099272.2	ENSP00000418751.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1672G>A (p.E558K) alteration is located in exon 12 (coding exon 10) of the BTBD9 gene. This alteration results from a G to A substitution at nucleotide position 1672, causing the glutamic acid (E) at amino acid position 558 to be replaced by a lysine (K). 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	0.22
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	.;T;T;.
Eigen	Benign	-0.013
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;.;D;D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.81	.;L;L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.32	N;N;.;N
REVEL	Benign	0.17
Sift	Uncertain	0.015	D;D;.;D
Sift4G	Uncertain	0.020	D;D;.;D
Polyphen		0.013	.;B;B;.
Vest4		0.22
MutPred		0.33		.;Gain of methylation at E558 (P = 7e-04);Gain of methylation at E558 (P = 7e-04);.;
MVP		0.76
MPC		0.84
ClinPred		0.93	D
GERP RS		5.3
Varity_R		0.19
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr6-38142928;