12-49842883-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181708.3(BCDIN3D):​c.205C>G​(p.Leu69Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCDIN3D NM_181708.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.90

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32321358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCDIN3D	NM_181708.3	c.205C>G	p.Leu69Val	missense_variant	Exon 1 of 2	ENST00000333924.6	NP_859059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCDIN3D	ENST00000333924.6	c.205C>G	p.Leu69Val	missense_variant	Exon 1 of 2	1	NM_181708.3	ENSP00000335201.4
BCDIN3D	ENST00000550861.1	n.212C>G		non_coding_transcript_exon_variant	Exon 1 of 2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.205C>G (p.L69V) alteration is located in exon 1 (coding exon 1) of the BCDIN3D gene. This alteration results from a C to G substitution at nucleotide position 205, causing the leucine (L) at amino acid position 69 to be replaced by a valine (V). 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	0.097
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0039	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.20
Sift	Benign	0.25	T
Sift4G	Benign	0.30	T
Polyphen		1.0	D
Vest4		0.33
MutPred		0.56		Gain of sheet (P = 0.0827);
MVP		0.42
MPC		0.13
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.65
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: rs1555154963; hg19: chr12-50236666; COSMIC: COSV61702309; COSMIC: COSV61702309;