10-122329521-G-C

Variant names:

• chr10-122329521-G-C
• rs2421013
• NM_144587.5:c.953G>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.953G>C​(p.Arg318Pro) 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. R318W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BTBD16 NM_144587.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 35 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=0.10144031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD16	NM_144587.5	c.953G>C	p.Arg318Pro	missense_variant	Exon 11 of 16	ENST00000260723.6	NP_653188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD16	ENST00000260723.6	c.953G>C	p.Arg318Pro	missense_variant	Exon 11 of 16	2	NM_144587.5	ENSP00000260723.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461676 Hom.: 0 Cov.: 50 AF XY: 0.00 AC XY: 0 AN XY: 727132

African (AFR) AF: 0.00 AC: 0 AN: 33478

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: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53234

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.5
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.055
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.0050	B
Vest4		0.18
MutPred		0.43		Loss of MoRF binding (P = 0.0454);
MVP		0.33
MPC		0.21
ClinPred		0.23	T
GERP RS		4.6
Varity_R		0.33
gMVP		0.73
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2421013; hg19: chr10-124089036;