10-122276792-A-C

Variant names:

• chr10-122276792-A-C
• NM_144587.5:c.20A>C

Variant summary

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

The NM_144587.5(BTBD16):​c.20A>C​(p.His7Pro) variant causes a missense, splice region 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. 17/23 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H7Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: BTBD16 NM_144587.5 missense, splice_region
• Scores: Splicing: ADA: 0.0001747
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.107
• Publications: 0 publications found

Genes affected

BTBD16 (HGNC:26340): (BTB domain containing 16) This gene encodes a protein that contains a BTB/POZ domain. This domain mediates protein-protein interactions. A mutation in this gene may be associated with bipolar disorder. [provided by RefSeq, Sep 2016]

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=0.19905466).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144587.5. 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
	BTBD16	NM_144587.5	MANE Select	c.20A>C	p.His7Pro	missense splice_region	Exon 3 of 16	NP_653188.2	Q32M84-1
	BTBD16	NM_001318189.3		c.23A>C	p.His8Pro	missense	Exon 3 of 16	NP_001305118.1	Q32M84-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD16	ENST00000260723.6	TSL:2 MANE Select	c.20A>C	p.His7Pro	missense splice_region	Exon 3 of 16	ENSP00000260723.4	Q32M84-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.3
DANN	Benign	0.85
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.11
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.061
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.048	D
Polyphen		0.80	P
Vest4		0.29
MutPred		0.27		Gain of loop (P = 0.0097)
MVP		0.36
MPC		0.23
ClinPred		0.34	T
GERP RS		0.69
Varity_R		0.14
gMVP		0.12
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
SpliceAI score (max)		0.030		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

hg19: chr10-124036307;