Genetic Variant NM_144587.5:c.953G>A (chr10-122329521-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144587.5(BTBD16):c.953G>A(p.Arg318Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,613,140 control chromosomes in the GnomAD database, including 231,016 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. R318W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.56 ( 23813 hom., cov: 33)

Exomes 𝑓: 0.53 ( 207203 hom. )

Consequence

BTBD16
NM_144587.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.46

Publications

35 publications found

Variant links:

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]

BTBD16 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1026592E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD16	NM_144587.5 link	c.953G>A	p.Arg318Gln	missense_variant	Exon 11 of 16	ENST00000260723.6	NP_653188.2	Q32M84-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD16	ENST00000260723.6 link	c.953G>A	p.Arg318Gln	missense_variant	Exon 11 of 16	2	NM_144587.5	ENSP00000260723.4		Q32M84-1

Frequencies

GnomAD3 genomes

AF:

0.555

AC:

84389

AN:

151922

Hom.:

23784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.604

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.572

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.864

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.588

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.540

GnomAD2 exomes

AF:

0.563

AC:

141297

AN:

251054

AF XY:

0.552

show subpopulations

Gnomad AFR exome

AF:

0.608

Gnomad AMR exome

AF:

0.628

Gnomad ASJ exome

AF:

0.514

Gnomad EAS exome

AF:

0.860

Gnomad FIN exome

AF:

0.593

Gnomad NFE exome

AF:

0.506

Gnomad OTH exome

AF:

0.542

GnomAD4 exome

AF:

0.528

AC:

770788

AN:

1461100

Hom.:

207203

Cov.:

AF XY:

0.526

AC XY:

382126

AN XY:

726872

show subpopulations

African (AFR)

AF:

0.601

AC:

20101

AN:

33466

American (AMR)

AF:

0.617

AC:

27579

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

13526

AN:

26120

East Asian (EAS)

AF:

0.886

AC:

35168

AN:

39688

South Asian (SAS)

AF:

0.497

AC:

42889

AN:

86212

European-Finnish (FIN)

AF:

0.588

AC:

31276

AN:

53172

Middle Eastern (MID)

AF:

0.581

AC:

3348

AN:

5762

European-Non Finnish (NFE)

AF:

0.507

AC:

563934

AN:

1111612

Other (OTH)

AF:

0.546

AC:

32967

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

18357

36715

55072

73430

91787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16516

33032

49548

66064

82580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.556

AC:

84459

AN:

152040

Hom.:

23813

Cov.:

AF XY:

0.561

AC XY:

41696

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.603

AC:

25018

AN:

41456

American (AMR)

AF:

0.572

AC:

8743

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

1765

AN:

3472

East Asian (EAS)

AF:

0.864

AC:

4463

AN:

5164

South Asian (SAS)

AF:

0.507

AC:

2444

AN:

4824

European-Finnish (FIN)

AF:

0.588

AC:

6223

AN:

10582

Middle Eastern (MID)

AF:

0.541

AC:

157

AN:

290

European-Non Finnish (NFE)

AF:

0.502

AC:

34110

AN:

67944

Other (OTH)

AF:

0.545

AC:

1151

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1952

3905

5857

7810

9762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.528

Hom.:

74621

Bravo

AF:

0.563

TwinsUK

AF:

0.502

AC:

1863

ALSPAC

AF:

0.498

AC:

1919

ESP6500AA

AF:

0.605

AC:

2667

ESP6500EA

AF:

0.511

AC:

4394

ExAC

AF:

0.561

AC:

68083

Asia WGS

AF:

0.686

AC:

2384

AN:

3478

EpiCase

AF:

0.502

EpiControl

AF:

0.512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.0

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0010

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.0

PhyloP100

1.5

PrimateAI

Benign

0.34

PROVEAN

Benign

1.9

REVEL

Benign

0.055

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.015

MPC

0.16

ClinPred

0.0038

GERP RS

4.6

Varity_R

0.028

gMVP

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over