15-83020707-G-A

Variant summary

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

The NM_025238.4(BTBD1):c.1111C>T(p.His371Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: BTBD1 NM_025238.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.68

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]

(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	UniProt
BTBD1	NM_025238.4	c.1111C>T	p.His371Tyr	missense_variant	6/8	ENST00000261721.9
LOC124903542	XR_007064742.1	n.1319+7648G>A		intron_variant, non_coding_transcript_variant
BTBD1	NM_001011885.2	c.1056-1854C>T		intron_variant
BTBD1	XR_007064459.1	n.1325C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTBD1	ENST00000261721.9	c.1111C>T	p.His371Tyr	missense_variant	6/8	1	NM_025238.4	P1
	ENST00000616598.1	n.593G>A		non_coding_transcript_exon_variant	1/1
	ENST00000566841.1	n.735-82717G>A		intron_variant, non_coding_transcript_variant		5
	ENST00000570202.1	n.62+7985G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

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

Jun 05, 2023

The c.1111C>T (p.H371Y) alteration is located in exon 6 (coding exon 6) of the BTBD1 gene. This alteration results from a C to T substitution at nucleotide position 1111, causing the histidine (H) at amino acid position 371 to be replaced by a tyrosine (Y). 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	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
Cadd	Uncertain	25
Dann	Benign	0.89
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.029
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.46
Sift	Benign	0.93	T
Sift4G	Benign	0.38	T
Polyphen		0.0090	B
Vest4		0.75
MutPred		0.55		Gain of sheet (P = 0.0028);
MVP		0.76
MPC		0.58
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.37
gMVP		0.37

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: chr15-83689459;