12-49839006-C-T

Variant summary

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

The NM_181708.3(BCDIN3D):​c.244G>A​(p.Val82Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,612,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

BCDIN3D
NM_181708.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26
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=0.11791003).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCDIN3DNM_181708.3 linkc.244G>A p.Val82Met missense_variant Exon 2 of 2 ENST00000333924.6 NP_859059.1 Q7Z5W3
BCDIN3D-AS1NR_027499.1 linkn.940C>T non_coding_transcript_exon_variant Exon 3 of 3
BCDIN3D-AS1NR_027501.1 linkn.936C>T non_coding_transcript_exon_variant Exon 3 of 3
BCDIN3D-AS1NR_027500.1 linkn.570+366C>T intron_variant Intron 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCDIN3DENST00000333924.6 linkc.244G>A p.Val82Met missense_variant Exon 2 of 2 1 NM_181708.3 ENSP00000335201.4 Q7Z5W3

Frequencies

GnomAD3 genomes
AF:
0.000223
AC:
34
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000128
AC:
32
AN:
250258
Hom.:
0
AF XY:
0.000148
AC XY:
20
AN XY:
135228
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:
0.00
Gnomad FIN exome
AF:
0.0000467
Gnomad NFE exome
AF:
0.000265
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000210
AC:
307
AN:
1460096
Hom.:
0
Cov.:
31
AF XY:
0.000193
AC XY:
140
AN XY:
726230
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000113
Gnomad4 NFE exome
AF:
0.000261
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000223
AC:
34
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000304
Hom.:
0
Bravo
AF:
0.000189
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.000436
EpiControl
AF:
0.000356

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 28, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.244G>A (p.V82M) alteration is located in exon 2 (coding exon 2) of the BCDIN3D gene. This alteration results from a G to A substitution at nucleotide position 244, causing the valine (V) at amino acid position 82 to be replaced by a methionine (M). 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
0.15
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
23
DANN
Benign
0.97
DEOGEN2
Benign
0.0021
T
Eigen
Benign
-0.052
Eigen_PC
Benign
0.028
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.95
N
REVEL
Benign
0.033
Sift
Benign
0.11
T
Sift4G
Benign
0.13
T
Polyphen
0.59
P
Vest4
0.29
MVP
0.44
MPC
0.14
ClinPred
0.11
T
GERP RS
3.0
Varity_R
0.13
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs147945649; hg19: chr12-50232789; API