chr15-83041826-T-C

Position:

• chr15-83041826-T-C

Variant summary

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

The NM_025238.4(BTBD1):​c.764A>G​(p.Gln255Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BTBD1 NM_025238.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.87

Genes affected

BTBD1 (HGNC:1120): (BTB domain containing 1) The C-terminus of the protein encoded by this gene binds topoisomerase I. The N-terminus contains a proline-rich region and a BTB/POZ domain (broad-complex, Tramtrack and bric a brac/Pox virus and Zinc finger), both of which are typically involved in protein-protein interactions. Subcellularly, the protein localizes to cytoplasmic bodies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

BTBD1 (HGNC:):

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
BTBD1	NM_025238.4	c.764A>G	p.Gln255Arg	missense_variant	4/8	ENST00000261721.9	NP_079514.1
BTBD1	NM_001011885.2	c.764A>G	p.Gln255Arg	missense_variant	4/7		NP_001011885.1
BTBD1	XR_007064459.1	n.865A>G		non_coding_transcript_exon_variant	4/7
LOC124903542	XR_007064742.1	n.1320-19661T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD1	ENST00000261721.9	c.764A>G	p.Gln255Arg	missense_variant	4/8	1	NM_025238.4	ENSP00000261721.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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 12, 2024

The c.764A>G (p.Q255R) alteration is located in exon 4 (coding exon 4) of the BTBD1 gene. This alteration results from a A to G substitution at nucleotide position 764, causing the glutamine (Q) at amino acid position 255 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-0.094
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.13	N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.56	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.47	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.013	B;.
Vest4		0.81
MutPred		0.49		Gain of MoRF binding (P = 0.0489);Gain of MoRF binding (P = 0.0489);
MVP		0.72
MPC		0.54
ClinPred		0.60	D
GERP RS		5.6
Varity_R		0.21
gMVP		0.72

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: chr15-83710578;