1-92102564-C-G

Position:

• chr1-92102564-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001376131.1(BTBD8):​c.439C>G​(p.Leu147Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 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: BTBD8 NM_001376131.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.640

Genes affected

BTBD8 (HGNC:21019): (BTB domain containing 8) Predicted to be involved in clathrin-dependent synaptic vesicle endocytosis; neuron projection development; and synaptic vesicle budding from endosome. Located in nucleoplasm. Colocalizes with AP-2 adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

BTBD8 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06267813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD8	NM_001376131.1	c.439C>G	p.Leu147Val	missense_variant	3/18	ENST00000636805.2	NP_001363060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD8	ENST00000636805.2	c.439C>G	p.Leu147Val	missense_variant	3/18	5	NM_001376131.1	ENSP00000490161.1
BTBD8	ENST00000342818.4	c.439C>G	p.Leu147Val	missense_variant	3/9	1		ENSP00000343686.3
BTBD8	ENST00000370382.7	n.706C>G		non_coding_transcript_exon_variant	3/6	1
BTBD8	ENST00000635934.1	n.439C>G		non_coding_transcript_exon_variant	3/17	5		ENSP00000490386.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Oct 08, 2024

The c.439C>G (p.L147V) alteration is located in exon 3 (coding exon 3) of the BTBD8 gene. This alteration results from a C to G substitution at nucleotide position 439, causing the leucine (L) at amino acid position 147 to be replaced by a valine (V). 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	0.066
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.91
DANN	Benign	0.38
DEOGEN2	Benign	0.0037	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.090	.;N
REVEL	Benign	0.026
Sift	Benign	0.87	.;T
Sift4G	Benign	0.55	.;T
Polyphen		0.061	.;B
Vest4		0.067
MutPred		0.45		Loss of catalytic residue at L147 (P = 0.025);Loss of catalytic residue at L147 (P = 0.025);
MVP		0.64
MPC		0.24
ClinPred		0.040	T
GERP RS		-0.034
Varity_R		0.046

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: chr1-92568121;