10-122336546-A-C

Position:

• chr10-122336546-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144587.5(BTBD16):​c.1316A>C​(p.His439Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,608,328 control chromosomes in the GnomAD database, including 102,119 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (10683 hom., cov: 33)
  • Exomes 𝑓: 0.34 (91436 hom.)
• Consequence: BTBD16 NM_144587.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.5271257E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD16	NM_144587.5	c.1316A>C	p.His439Pro	missense_variant	15/16	ENST00000260723.6	NP_653188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD16	ENST00000260723.6	c.1316A>C	p.His439Pro	missense_variant	15/16	2	NM_144587.5	ENSP00000260723	P1
BTBD16	ENST00000495370.2	n.522A>C		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55669 AN: 151870 Hom.: 10656 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.353

GnomAD3 exomes AF: 0.397 AC: 98377 AN: 247864 Hom.: 21432 AF XY: 0.390 AC XY: 52306 AN XY: 134182

Gnomad AFR exome AF: 0.362

Gnomad AMR exome AF: 0.530

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.687

Gnomad SAS exome AF: 0.413

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.319

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.343 AC: 498943 AN: 1456340 Hom.: 91436 Cov.: 35 AF XY: 0.344 AC XY: 249150 AN XY: 724656

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.739

Gnomad4 SAS exome AF: 0.409

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.367 AC: 55735 AN: 151988 Hom.: 10683 Cov.: 33 AF XY: 0.376 AC XY: 27953 AN XY: 74302

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.361

Alfa AF: 0.324 Hom.: 15423

Bravo AF: 0.370

TwinsUK AF: 0.308 AC: 1142

ALSPAC AF: 0.297 AC: 1145

ESP6500AA AF: 0.359 AC: 1583

ESP6500EA AF: 0.322 AC: 2766

ExAC AF: 0.394 AC: 47885

Asia WGS AF: 0.566 AC: 1968 AN: 3478

EpiCase AF: 0.315

EpiControl AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.20
DANN	Benign	0.39
DEOGEN2	Benign	0.00098	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00088	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0000055	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.4	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.024
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.044
MPC		0.22
ClinPred		0.0067	T
GERP RS		1.4
Varity_R		0.054
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs1048347; hg19: chr10-124096061; COSMIC: COSV53262086;