12-49838637-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.613G>A​(p.Ala205Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

BCDIN3D
NM_181708.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88
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=0.0897463).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCDIN3DNM_181708.3 linkc.613G>A p.Ala205Thr missense_variant Exon 2 of 2 ENST00000333924.6 NP_859059.1 Q7Z5W3
BCDIN3D-AS1NR_027499.1 linkn.571C>T non_coding_transcript_exon_variant Exon 3 of 3
BCDIN3D-AS1NR_027500.1 linkn.567C>T non_coding_transcript_exon_variant Exon 3 of 4
BCDIN3D-AS1NR_027501.1 linkn.567C>T non_coding_transcript_exon_variant Exon 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCDIN3DENST00000333924.6 linkc.613G>A p.Ala205Thr missense_variant Exon 2 of 2 1 NM_181708.3 ENSP00000335201.4 Q7Z5W3

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000281
AC:
7
AN:
248960
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134768
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.0000289
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:
0.00000616
AC:
9
AN:
1461566
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727012
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000854
AC:
13
AN:
152266
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.00
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
Alfa
AF:
0.000198
Hom.:
0
Bravo
AF:
0.000125
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.613G>A (p.A205T) 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 613, causing the alanine (A) at amino acid position 205 to be replaced by a threonine (T). 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
-0.34
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0027
T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.090
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.95
L
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
0.52
N
REVEL
Benign
0.14
Sift
Benign
0.47
T
Sift4G
Benign
0.93
T
Polyphen
1.0
D
Vest4
0.34
MVP
0.33
MPC
0.31
ClinPred
0.14
T
GERP RS
5.3
Varity_R
0.16
gMVP
0.63

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.

Other links and lift over

dbSNP: rs146267903; hg19: chr12-50232420; API