11-57744712-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145101.3(BTBD18):c.1561G>C(p.Gly521Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000664 in 1,551,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

BTBD18
NM_001145101.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.381

Variant links:

Genes affected

BTBD18 (HGNC:37214): (BTB domain containing 18) Predicted to be involved in several processes, including male gamete generation; piRNA biosynthetic process; and positive regulation of transcription elongation from RNA polymerase II promoter. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

BTBD18 links:

ENSG00000254732 (HGNC:):

ENSG00000254732 links:

TMX2-CTNND1 (HGNC:41992): (TMX2-CTNND1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring TMX2 (thioredoxin-related transmembrane protein 2) and CTNND1 (catenin, cadherin-associated protein, delta 1) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

TMX2-CTNND1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07776362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD18	NM_001145101.3 link	c.1561G>C	p.Gly521Arg	missense_variant	Exon 3 of 3	ENST00000422652.6	NP_001138573.1	B2RXH4
BTBD18	XM_017018128.2 link	c.1561G>C	p.Gly521Arg	missense_variant	Exon 3 of 3		XP_016873617.1	B2RXH4
BTBD18	XM_047427405.1 link	c.1561G>C	p.Gly521Arg	missense_variant	Exon 4 of 4		XP_047283361.1
TMX2-CTNND1	NR_037646.1 link	n.346+7044C>G		intron_variant	Intron 2 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BTBD18	ENST00000422652.6 link	c.1561G>C	p.Gly521Arg	missense_variant	Exon 3 of 3	4	NM_001145101.3	ENSP00000394472.1	B2RXH4
ENSG00000254732	ENST00000531074.1 link	n.*152+1728C>G		intron_variant	Intron 2 of 3	3		ENSP00000457993.1	H3BV83
ENSG00000288534	ENST00000674060.1 link	n.103+7044C>G		intron_variant	Intron 2 of 19			ENSP00000501055.2	A0A669KB09

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

154014

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

81718

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:

0.000571

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000335

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1399406

Hom.:

Cov.:

AF XY:

0.0000855

AC XY:

AN XY:

690214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000669

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000204

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000212

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 21, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1561G>C (p.G521R) alteration is located in exon 3 (coding exon 2) of the BTBD18 gene. This alteration results from a G to C substitution at nucleotide position 1561, causing the glycine (G) at amino acid position 521 to be replaced by an arginine (R). 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

0.17

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.0099

Eigen_PC

Benign

-0.073

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.76

.;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.0

L;L

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.85

N;N

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

0.96

D;D

Vest4

0.38

MutPred

0.29

Gain of catalytic residue at G521 (P = 0.0667);Gain of catalytic residue at G521 (P = 0.0667);

MVP

0.43

ClinPred

0.16

GERP RS

3.4

Varity_R

0.11

gMVP

0.14

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