Genetic Variant BTBD16:p.Thr103Ile (chr10-122286171-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144587.5(BTBD16):c.308C>T(p.Thr103Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

BTBD16
NM_144587.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD16	NM_144587.5 link	c.308C>T	p.Thr103Ile	missense_variant	Exon 5 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.308C>T	p.Thr103Ile	missense_variant	Exon 5 of 16	2	NM_144587.5	ENSP00000260723.4		Q32M84-1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000199

AC:

AN:

251440

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000401

AC:

586

AN:

1461720

Hom.:

Cov.:

AF XY:

0.000395

AC XY:

287

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000486

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000223

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000318

Hom.:

Bravo

AF:

0.000272

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.308C>T (p.T103I) alteration is located in exon 5 (coding exon 4) of the BTBD16 gene. This alteration results from a C to T substitution at nucleotide position 308, causing the threonine (T) at amino acid position 103 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.78

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.25

Sift

Benign

0.061

Sift4G

Uncertain

0.043

Polyphen

0.97

Vest4

0.76

MVP

0.50

MPC

0.64

ClinPred

0.25

GERP RS

4.9

Varity_R

0.18

gMVP

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over