Genetic Variant BTBD19:p.Trp200Arg (chr1-44813252-T-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001136537.3(BTBD19):c.598T>C(p.Trp200Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BTBD19
NM_001136537.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

Publications

0 publications found

Variant links:

Genes affected

BTBD19 (HGNC:27145): (BTB domain containing 19)

BTBD19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.982

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136537.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTBD19	NM_001136537.3	MANE Select	c.598T>C	p.Trp200Arg	missense	Exon 6 of 8	NP_001130009.1	C9JJ37-1
BTBD19	NM_001394561.1		c.859T>C	p.Trp287Arg	missense	Exon 5 of 7	NP_001381490.1
BTBD19	NM_001394562.1		c.661T>C	p.Trp221Arg	missense	Exon 6 of 8	NP_001381491.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTBD19	ENST00000450269.6	TSL:5 MANE Select	c.598T>C	p.Trp200Arg	missense	Exon 6 of 8	ENSP00000395461.1	C9JJ37-1
BTBD19	ENST00000409335.6	TSL:5	c.484T>C	p.Trp162Arg	missense	Exon 4 of 6	ENSP00000386506.2	A0A0A0MSF5
BTBD19	ENST00000718238.1		c.484T>C	p.Trp162Arg	missense	Exon 4 of 6	ENSP00000520683.1	A0A0A0MSF5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1382798

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

681482

African (AFR)

AF:

0.00

AC:

AN:

31386

American (AMR)

AF:

0.00

AC:

AN:

35044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24894

East Asian (EAS)

AF:

0.00

AC:

AN:

35522

South Asian (SAS)

AF:

0.00

AC:

AN:

78808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38984

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074922

Other (OTH)

AF:

0.00

AC:

AN:

57560

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.67

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.73

MetaRNN

Pathogenic

0.98

MetaSVM

Pathogenic

0.82

MutationAssessor

Pathogenic

3.5

PhyloP100

5.3

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-14

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.93

MutPred

0.77

Gain of disorder (P = 1e-04)

MVP

0.48

ClinPred

1.0

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.72

gMVP

0.84

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over