chr6-38175152-C-T

Variant names:

• chr6-38175152-C-T
• NM_001099272.2:c.1672G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20927334).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099272.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD9	NM_001099272.2	MANE Select	c.1672G>A	p.Glu558Lys	missense	Exon 11 of 11	NP_001092742.1	Q96Q07-1
	BTBD9	NM_052893.2		c.1672G>A	p.Glu558Lys	missense	Exon 12 of 12	NP_443125.1	Q96Q07-1
	BTBD9	NM_001172418.2		c.1582G>A	p.Glu528Lys	missense	Exon 11 of 11	NP_001165889.1	Q96Q07-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD9	ENST00000481247.6	TSL:5 MANE Select	c.1672G>A	p.Glu558Lys	missense	Exon 11 of 11	ENSP00000418751.1	Q96Q07-1
	BTBD9	ENST00000419706.6	TSL:1	c.1582G>A	p.Glu528Lys	missense	Exon 11 of 11	ENSP00000415365.2	Q96Q07-2
	BTBD9	ENST00000314100.10	TSL:1	c.1468G>A	p.Glu490Lys	missense	Exon 10 of 10	ENSP00000323408.6	Q96Q07-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.013
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.17
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.020	D
Polyphen		0.013	B
Vest4		0.22
MutPred		0.33		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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr6-38142928;