chr12-49838936-C-A

Variant summary

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

The NM_181708.3(BCDIN3D):​c.314G>T​(p.Arg105Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R105H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BCDIN3D
NM_181708.3 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.56
Variant links:
Genes affected
BCDIN3D (HGNC:27050): (BCDIN3 domain containing RNA methyltransferase) This gene encodes an RNA methyltransferase which belongs to the rossmann fold methyltransferase family, and serves as a 5'-methylphosphate capping enzyme that is specific for cytoplasmic histidyl tRNA. The encoded protein contains an S-adenosylmethionine binding domain and uses the methyl group donor, S-adenosylmethionine. This gene is overexpressed in breast cancer cells, and is related to the tumorigenic phenotype and poor prognosis of breast cancer. The encoded protein is thought to promote the cellular invasion of breast cancer cells, by downregulating the expression of tumor suppressor miRNAs through the dimethylation of the 5-monophosphate of the corresponding precursor miRNAs. [provided by RefSeq, Apr 2017]
BCDIN3D-AS1 (HGNC:44113): (BCDIN3D antisense RNA 1)

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=0.17972282).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCDIN3DNM_181708.3 linkc.314G>T p.Arg105Leu missense_variant Exon 2 of 2 ENST00000333924.6 NP_859059.1 Q7Z5W3
BCDIN3D-AS1NR_027499.1 linkn.870C>A non_coding_transcript_exon_variant Exon 3 of 3
BCDIN3D-AS1NR_027501.1 linkn.866C>A non_coding_transcript_exon_variant Exon 3 of 3
BCDIN3D-AS1NR_027500.1 linkn.570+296C>A intron_variant Intron 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCDIN3DENST00000333924.6 linkc.314G>T p.Arg105Leu missense_variant Exon 2 of 2 1 NM_181708.3 ENSP00000335201.4 Q7Z5W3

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152098
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250690
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135586
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461870
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152098
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.086
T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.079
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Benign
0.23
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.14
Sift
Benign
0.064
T
Sift4G
Benign
0.20
T
Polyphen
0.24
B
Vest4
0.27
MutPred
0.42
Gain of helix (P = 0.0078);
MVP
0.60
MPC
0.22
ClinPred
0.77
D
GERP RS
2.3
Varity_R
0.38
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs200103513; hg19: chr12-50232719; API