12-49843065-T-C

Position:

• chr12-49843065-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000333924.6(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 ENST00000333924.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.186

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]

ACMG classification

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/exons	MANE	Protein	UniProt
BCDIN3D	NM_181708.3	c.23A>G	p.Asp8Gly	missense_variant	1/2	ENST00000333924.6	NP_859059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCDIN3D	ENST00000333924.6	c.23A>G	p.Asp8Gly	missense_variant	1/2	1	NM_181708.3	ENSP00000335201	P1
BCDIN3D	ENST00000550861.1	n.30A>G		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.00601 AC: 915 AN: 152176 Hom.: 32 Cov.: 32

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.: 97 AF XY: 0.00785 AC XY: 1064 AN XY: 135510

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.: 31 AF XY: 0.00202 AC XY: 1472 AN XY: 727088

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.: 35 Cov.: 32 AF XY: 0.00705 AC XY: 525 AN XY: 74468

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.: 2

Bravo AF: 0.00845

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00737 AC: 894

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 05, 2018	- -

Oromandibular-limb hypogenesis spectrum Benign:1

Likely benign, no assertion criteria provided

research

CHU Sainte-Justine Research Center, University of Montreal

Aug 12, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.8
DANN	Benign	0.47
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.12
Sift	Benign	0.26	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.26
MPC		0.17
ClinPred		0.011	T
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

Other links and lift over

dbSNP: rs143608766; hg19: chr12-50236848;