20-11923006-G-T

Variant names:

• chr20-11923006-G-T
• rs35364034
• NM_014962.4:c.909G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014962.4(BTBD3):​c.909G>T​(p.Ala303Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A303A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BTBD3 NM_014962.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908
• Publications: 11 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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-0.908 with no splicing effect.

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.909G>T	p.Ala303Ala	synonymous	Exon 4 of 4	NP_055777.1	Q9Y2F9-1
	BTBD3	NM_001395005.1		c.909G>T	p.Ala303Ala	synonymous	Exon 5 of 5	NP_001381934.1	Q9Y2F9-1
	BTBD3	NM_001395006.1		c.909G>T	p.Ala303Ala	synonymous	Exon 5 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.909G>T	p.Ala303Ala	synonymous	Exon 4 of 4	ENSP00000367471.2	Q9Y2F9-1
	BTBD3	ENST00000618296.4	TSL:1	c.726G>T	p.Ala242Ala	synonymous	Exon 5 of 5	ENSP00000477589.1	Q9Y2F9-2
	BTBD3	ENST00000405977.5	TSL:5	c.909G>T	p.Ala303Ala	synonymous	Exon 5 of 5	ENSP00000384545.1	Q9Y2F9-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.84
PhyloP100		-0.91

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: rs35364034; hg19: chr20-11903654;