20-11918559-C-A

Variant names:

• chr20-11918559-C-A
• rs553845593
• NM_014962.4:c.284C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014962.4(BTBD3):​c.284C>A​(p.Pro95Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P95L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BTBD3 NM_014962.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.60
• Publications: 2 publications found

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:40728): (BTBD3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24565509).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014962.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD3	NM_014962.4	MANE Select	c.284C>A	p.Pro95Gln	missense	Exon 1 of 4	NP_055777.1	Q9Y2F9-1
	BTBD3	NM_001395005.1		c.284C>A	p.Pro95Gln	missense	Exon 2 of 5	NP_001381934.1	Q9Y2F9-1
	BTBD3	NM_001395006.1		c.284C>A	p.Pro95Gln	missense	Exon 2 of 5	NP_001381935.1	Q9Y2F9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD3	ENST00000378226.7	TSL:1 MANE Select	c.284C>A	p.Pro95Gln	missense	Exon 1 of 4	ENSP00000367471.2	Q9Y2F9-1
	BTBD3	ENST00000618296.4	TSL:1	c.101C>A	p.Pro34Gln	missense	Exon 2 of 5	ENSP00000477589.1	Q9Y2F9-2
	BTBD3-AS1	ENST00000439529.1	TSL:1	n.119G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249534 AF XY: 0.00000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460416 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726456

African (AFR) AF: 0.00 AC: 0 AN: 33318

American (AMR) AF: 0.00 AC: 0 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 85990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111512

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.14	N
PhyloP100		4.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.50	N
REVEL	Uncertain	0.31
Sift	Benign	0.25	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.35		Loss of glycosylation at P95 (P = 0.1851)
MVP		0.86
MPC		0.63
ClinPred		0.30	T
GERP RS		6.2
PromoterAI		0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.15
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs553845593; hg19: chr20-11899207;