NM_144587.5:c.1316A>G

Variant names:

• chr10-122336546-A-G
• rs1048347
• NM_144587.5:c.1316A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144587.5(BTBD16):​c.1316A>G​(p.His439Arg) variant causes a missense 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. 16/22 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. H439N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BTBD16 NM_144587.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 26 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04993248).

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.1316A>G	p.His439Arg	missense	Exon 15 of 16	NP_653188.2	Q32M84-1
	BTBD16	NM_001318189.3		c.1319A>G	p.His440Arg	missense	Exon 15 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.1316A>G	p.His439Arg	missense	Exon 15 of 16	ENSP00000260723.4	Q32M84-1
	BTBD16	ENST00000495370.2	TSL:3	n.522A>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.0
DANN	Benign	0.77
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.091
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.024
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.023	D
Polyphen		0.0	B
Vest4		0.043
MutPred		0.46		Gain of MoRF binding (P = 0.0084)
MVP		0.15
MPC		0.17
ClinPred		0.10	T
GERP RS		1.4
Varity_R		0.038
gMVP		0.15
Mutation Taster		=100/0	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: rs1048347; hg19: chr10-124096061;