chr10-122336546-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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: 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
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
BTBD16	NM_144587.5	c.1316A>C	p.His439Pro	missense_variant	Exon 15 of 16	ENST00000260723.6	NP_653188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD16	ENST00000260723.6	c.1316A>C	p.His439Pro	missense_variant	Exon 15 of 16	2	NM_144587.5	ENSP00000260723.4
BTBD16	ENST00000495370.2	n.522A>C		non_coding_transcript_exon_variant	Exon 4 of 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

GnomAD2 exomes AF: 0.397 AC: 98377 AN: 247864 AF XY: 0.390

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 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

African (AFR) AF: 0.365 AC: 12106 AN: 33198

American (AMR) AF: 0.516 AC: 22495 AN: 43632

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 7639 AN: 26034

East Asian (EAS) AF: 0.739 AC: 29202 AN: 39536

South Asian (SAS) AF: 0.409 AC: 34989 AN: 85612

European-Finnish (FIN) AF: 0.422 AC: 22500 AN: 53344

Middle Eastern (MID) AF: 0.364 AC: 2095 AN: 5762

European-Non Finnish (NFE) AF: 0.312 AC: 346304 AN: 1108998

Other (OTH) AF: 0.359 AC: 21613 AN: 60224

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

African (AFR) AF: 0.364 AC: 15089 AN: 41434

American (AMR) AF: 0.446 AC: 6804 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3468

East Asian (EAS) AF: 0.694 AC: 3577 AN: 5156

South Asian (SAS) AF: 0.417 AC: 2009 AN: 4812

European-Finnish (FIN) AF: 0.418 AC: 4421 AN: 10572

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21799 AN: 67972

Other (OTH) AF: 0.361 AC: 761 AN: 2108

Alfa AF: 0.334 Hom.: 37223

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
PhyloP100		0.091
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
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV53262086;