NM_001099272.2:c.1532T>C

Variant names:

• chr6-38256439-A-G
• rs376734377
• NM_001099272.2:c.1532T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001099272.2(BTBD9):​c.1532T>C​(p.Met511Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,613,752 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M511V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000063 (1 hom.)
• Consequence: BTBD9 NM_001099272.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20
• Publications: 1 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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29742467).

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.1532T>C	p.Met511Thr	missense	Exon 9 of 11	NP_001092742.1	Q96Q07-1
	BTBD9	NM_052893.2		c.1532T>C	p.Met511Thr	missense	Exon 10 of 12	NP_443125.1	Q96Q07-1
	BTBD9	NM_001172418.2		c.1442T>C	p.Met481Thr	missense	Exon 9 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.1532T>C	p.Met511Thr	missense	Exon 9 of 11	ENSP00000418751.1	Q96Q07-1
	BTBD9	ENST00000419706.6	TSL:1	c.1442T>C	p.Met481Thr	missense	Exon 9 of 11	ENSP00000415365.2	Q96Q07-2
	BTBD9	ENST00000314100.10	TSL:1	c.1328T>C	p.Met443Thr	missense	Exon 8 of 10	ENSP00000323408.6	Q96Q07-3

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152242 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000481 AC: 12 AN: 249266 AF XY: 0.0000518

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000707

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000630 AC: 92 AN: 1461392 Hom.: 1 Cov.: 30 AF XY: 0.0000605 AC XY: 44 AN XY: 727040

African (AFR) AF: 0.000119 AC: 4 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5762

European-Non Finnish (NFE) AF: 0.0000603 AC: 67 AN: 1111590

Other (OTH) AF: 0.000132 AC: 8 AN: 60380

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152360 Hom.: 0 Cov.: 31 AF XY: 0.0000671 AC XY: 5 AN XY: 74512

African (AFR) AF: 0.0000240 AC: 1 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000662 AC: 8

EpiCase AF: 0.000382

EpiControl AF: 0.000178

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	0.17
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	22
DANN	Benign	0.83
DEOGEN2	Uncertain	0.68	D
Eigen	Benign	0.0039
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.30	T
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Benign	0.41	N
PhyloP100		3.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.4	N
REVEL	Pathogenic	0.66
Sift	Benign	0.28	T
Sift4G	Benign	0.41	T
Polyphen		0.72	P
Vest4		0.46
MVP		0.95
MPC		0.42
ClinPred		0.12	T
GERP RS		5.0
Varity_R		0.28
gMVP		0.34
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs376734377; hg19: chr6-38224215;