20-11923491-C-G

Variant names:

• chr20-11923491-C-G
• rs77962945
• NM_014962.4:c.1394C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014962.4(BTBD3):​c.1394C>G​(p.Thr465Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. T465I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BTBD3 NM_014962.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40981692).

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.1394C>G	p.Thr465Ser	missense	Exon 4 of 4	NP_055777.1	Q9Y2F9-1
	BTBD3	NM_001395005.1		c.1394C>G	p.Thr465Ser	missense	Exon 5 of 5	NP_001381934.1	Q9Y2F9-1
	BTBD3	NM_001395006.1		c.1394C>G	p.Thr465Ser	missense	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.1394C>G	p.Thr465Ser	missense	Exon 4 of 4	ENSP00000367471.2	Q9Y2F9-1
	BTBD3	ENST00000618296.4	TSL:1	c.1211C>G	p.Thr404Ser	missense	Exon 5 of 5	ENSP00000477589.1	Q9Y2F9-2
	BTBD3	ENST00000405977.5	TSL:5	c.1394C>G	p.Thr465Ser	missense	Exon 5 of 5	ENSP00000384545.1	Q9Y2F9-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.36
Sift	Benign	0.077	T
Sift4G	Benign	0.10	T
Polyphen		0.037	B
Vest4		0.47
MutPred		0.52		Gain of sheet (P = 0.0827)
MVP		0.89
MPC		0.65
ClinPred		0.66	D
GERP RS		6.0
Varity_R		0.20
gMVP		0.15
Mutation Taster		=65/35	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: rs77962945; hg19: chr20-11904139;