11-57745035-C-A

Variant summary

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

The NM_001145101.3(BTBD18):​c.1238G>T​(p.Arg413Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BTBD18
NM_001145101.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.452
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]
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]

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=0.114414304).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BTBD18NM_001145101.3 linkc.1238G>T p.Arg413Ile missense_variant Exon 3 of 3 ENST00000422652.6 NP_001138573.1 B2RXH4
BTBD18XM_017018128.2 linkc.1238G>T p.Arg413Ile missense_variant Exon 3 of 3 XP_016873617.1 B2RXH4
BTBD18XM_047427405.1 linkc.1238G>T p.Arg413Ile missense_variant Exon 4 of 4 XP_047283361.1
TMX2-CTNND1NR_037646.1 linkn.346+7367C>A intron_variant Intron 2 of 20

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BTBD18ENST00000422652.6 linkc.1238G>T p.Arg413Ile missense_variant Exon 3 of 3 4 NM_001145101.3 ENSP00000394472.1 B2RXH4
ENSG00000254732ENST00000531074.1 linkn.*152+2051C>A intron_variant Intron 2 of 3 3 ENSP00000457993.1 H3BV83
ENSG00000288534ENST00000674060.1 linkn.103+7367C>A intron_variant Intron 2 of 19 ENSP00000501055.2 A0A669KB09

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000143
AC:
2
AN:
1399264
Hom.:
0
Cov.:
34
AF XY:
0.00000145
AC XY:
1
AN XY:
690130
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 06, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1238G>T (p.R413I) alteration is located in exon 3 (coding exon 2) of the BTBD18 gene. This alteration results from a G to T substitution at nucleotide position 1238, causing the arginine (R) at amino acid position 413 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
0.11
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
0.89
DANN
Benign
0.96
DEOGEN2
Benign
0.027
T;T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.55
.;T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
0.97
L;L
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.28
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.031
D;D
Polyphen
0.55
P;P
Vest4
0.22
MutPred
0.17
Loss of solvent accessibility (P = 0.0611);Loss of solvent accessibility (P = 0.0611);
MVP
0.30
ClinPred
0.35
T
GERP RS
2.1
Varity_R
0.062
gMVP
0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-57512507; API