11-111495282-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001367975.1(BTG4):c.543G>T(p.Trp181Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000224 in 1,610,132 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W181G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

BTG4
NM_001367975.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65

Publications

1 publications found

Variant links:

Genes affected

BTG4 (HGNC:13862): (BTG anti-proliferation factor 4) The protein encoded by this gene is a member of the BTG/Tob family. This family has structurally related proteins that appear to have antiproliferative properties. This encoded protein can induce G1 arrest in the cell cycle. [provided by RefSeq, Jul 2008]

BTG4 Gene-Disease associations (from GenCC):

oocyte maturation defect 8
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
female infertility
Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox

BTG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.855

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTG4	NM_001367975.1 link	c.543G>T	p.Trp181Cys	missense_variant	Exon 5 of 5	ENST00000692032.1	NP_001354904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BTG4	ENST00000692032.1 link	c.543G>T	p.Trp181Cys	missense_variant	Exon 5 of 5		NM_001367975.1	ENSP00000509850.1	A0A8I5KVE8
BTG4	ENST00000689553.1 link	c.543G>T	p.Trp181Cys	missense_variant	Exon 7 of 7			ENSP00000508793.1	A0A8I5KVE8
BTG4	ENST00000356018.6 link	c.543G>T	p.Trp181Cys	missense_variant	Exon 5 of 6	5		ENSP00000348300.2	Q9NY30-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151818

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000202

AC:

AN:

247564

AF XY:

0.0000149

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1458314

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33242

American (AMR)

AF:

0.00

AC:

AN:

43728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39598

South Asian (SAS)

AF:

0.00

AC:

AN:

85406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

1110844

Other (OTH)

AF:

0.0000166

AC:

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151818

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41272

American (AMR)

AF:

0.00

AC:

AN:

15236

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:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2088

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

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 14, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.543G>T (p.W181C) alteration is located in exon 5 (coding exon 4) of the BTG4 gene. This alteration results from a G to T substitution at nucleotide position 543, causing the tryptophan (W) at amino acid position 181 to be replaced by a cysteine (C). 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

Pathogenic

0.59

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.34

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.79

M_CAP

Benign

0.031

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

-0.10

MutationAssessor

Uncertain

2.7

PhyloP100

3.6

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.7

REVEL

Pathogenic

0.85

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.51

MutPred

0.72

Loss of MoRF binding (P = 0.0104);

MVP

0.46

MPC

0.38

ClinPred

0.98

GERP RS

5.0

Varity_R

0.51

gMVP

0.66

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-111495282-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over