chr15-83030239-T-G

Position:

• chr15-83030239-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025238.4(BTBD1):​c.952A>C​(p.Ile318Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTBD1 NM_025238.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.22

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2216447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD1	NM_025238.4	c.952A>C	p.Ile318Leu	missense_variant	5/8	ENST00000261721.9	NP_079514.1
BTBD1	NM_001011885.2	c.952A>C	p.Ile318Leu	missense_variant	5/7		NP_001011885.1
BTBD1	XR_007064459.1	n.1053A>C		non_coding_transcript_exon_variant	5/7
LOC124903542	XR_007064742.1	n.1319+17180T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD1	ENST00000261721.9	c.952A>C	p.Ile318Leu	missense_variant	5/8	1	NM_025238.4	ENSP00000261721.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Aug 27, 2024

The c.952A>C (p.I318L) alteration is located in exon 5 (coding exon 5) of the BTBD1 gene. This alteration results from a A to C substitution at nucleotide position 952, causing the isoleucine (I) at amino acid position 318 to be replaced by a leucine (L). 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	0.082
BayesDel_addAF	Benign	0.0042	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	0.0057
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.92	N;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.27	N;N
REVEL	Benign	0.26
Sift	Benign	0.37	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.0	B;.
Vest4		0.48
MutPred		0.41		Gain of disorder (P = 0.2226);Gain of disorder (P = 0.2226);
MVP		0.72
MPC		0.47
ClinPred		0.87	D
GERP RS		5.2
Varity_R		0.13
gMVP		0.31

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: chr15-83698991;