chr20-11918520-A-G

Position:

• chr20-11918520-A-G

Variant summary

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

The NM_014962.4(BTBD3):​c.245A>G​(p.Gln82Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BTBD3 NM_014962.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13

Genes affected

BTBD3 (HGNC:15854): (BTB domain containing 3) Enables identical protein binding activity. Predicted to be involved in cerebral cortex development and dendrite morphogenesis. Predicted to be located in nucleus. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

BTBD3-AS1 (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=0.22581276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD3	NM_014962.4	c.245A>G	p.Gln82Arg	missense_variant	1/4	ENST00000378226.7	NP_055777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD3	ENST00000378226.7	c.245A>G	p.Gln82Arg	missense_variant	1/4	1	NM_014962.4	ENSP00000367471.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Dec 19, 2022

The c.245A>G (p.Q82R) alteration is located in exon 1 (coding exon 1) of the BTBD3 gene. This alteration results from a A to G substitution at nucleotide position 245, causing the glutamine (Q) at amino acid position 82 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	0.12
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Benign	0.87
DEOGEN2	Benign	0.013	.;.;T;.;.;T;.
Eigen	Benign	-0.061
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.77	.;.;.;T;.;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.3	.;.;L;.;.;L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.28	N;N;N;N;.;N;.
REVEL	Benign	0.20
Sift	Benign	0.50	T;T;T;T;.;T;.
Sift4G	Benign	0.52	T;T;T;T;T;T;T
Polyphen		0.028	.;.;B;.;.;B;.
Vest4		0.36
MutPred		0.19		.;.;Gain of MoRF binding (P = 0.032);.;.;Gain of MoRF binding (P = 0.032);.;
MVP		0.86
MPC		0.75
ClinPred		0.44	T
GERP RS		5.1
Varity_R		0.24
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs1568614962; hg19: chr20-11899168;