12-49843065-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181708.3(BCDIN3D):c.23A>G(p.Asp8Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,613,930 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 35 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 119 hom. )

Consequence

BCDIN3D
NM_181708.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.186

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024388433).

BP6

Variant 12-49843065-T-C is Benign according to our data. Variant chr12-49843065-T-C is described in ClinVar as [Benign]. Clinvar id is 254103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCDIN3D	NM_181708.3 link	c.23A>G	p.Asp8Gly	missense_variant	Exon 1 of 2	ENST00000333924.6	NP_859059.1	Q7Z5W3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCDIN3D	ENST00000333924.6 link	c.23A>G	p.Asp8Gly	missense_variant	Exon 1 of 2	1	NM_181708.3	ENSP00000335201.4		Q7Z5W3
BCDIN3D	ENST00000550861.1 link	n.30A>G		non_coding_transcript_exon_variant	Exon 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.00601

AC:

915

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0509

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00509

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0106

AC:

2658

AN:

250384

Hom.:

AF XY:

0.00785

AC XY:

1064

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.000748

Gnomad AMR exome

AF:

0.0715

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00324

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00851

GnomAD4 exome

AF:

0.00242

AC:

3541

AN:

1461636

Hom.:

119

Cov.:

AF XY:

0.00202

AC XY:

1472

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.0687

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000765

Gnomad4 FIN exome

AF:

0.00296

Gnomad4 NFE exome

AF:

0.0000791

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00605

AC:

922

AN:

152294

Hom.:

Cov.:

AF XY:

0.00705

AC XY:

525

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.0513

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00509

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.000417

Hom.:

Bravo

AF:

0.00845

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00737

AC:

894

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oromandibular-limb hypogenesis spectrum

Benign:1

Aug 12, 2016

CHU Sainte-Justine Research Center, University of Montreal

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.8

DANN

Benign

0.47

DEOGEN2

Benign

0.0010

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.42

REVEL

Benign

0.12

Sift

Benign

0.26

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.26

MPC

0.17

ClinPred

0.011

GERP RS

-0.55

Varity_R

0.053

gMVP

0.53

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