12-49842883-G-T

Variant names:

• chr12-49842883-G-T
• rs1555154963
• NM_181708.3:c.205C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181708.3(BCDIN3D):​c.205C>A​(p.Leu69Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L69V) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: BCDIN3D NM_181708.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39562562).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181708.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCDIN3D	NM_181708.3	MANE Select	c.205C>A	p.Leu69Met	missense	Exon 1 of 2	NP_859059.1	Q7Z5W3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCDIN3D	ENST00000333924.6	TSL:1 MANE Select	c.205C>A	p.Leu69Met	missense	Exon 1 of 2	ENSP00000335201.4	Q7Z5W3
	BCDIN3D	ENST00000550861.1	TSL:5	n.212C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74374

African (AFR) AF: 0.0000241 AC: 1 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.0044	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.9
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.25
Sift	Benign	0.031	D
Sift4G	Uncertain	0.048	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.54		Gain of sheet (P = 0.0344)
MVP		0.47
MPC		0.15
ClinPred		0.86	D
GERP RS		5.2
PromoterAI		0.041	Neutral
Varity_R		0.65
gMVP		0.49
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs1555154963; hg19: chr12-50236666;