12-49838696-T-C

Variant names:

• chr12-49838696-T-C
• rs1946529422
• NM_181708.3:c.554A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181708.3(BCDIN3D):​c.554A>G​(p.His185Arg) 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. 16/22 in silico tools predict 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: 2.46
• 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]

BCDIN3D-AS1 (HGNC:44113): (BCDIN3D antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08322579).

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.554A>G	p.His185Arg	missense	Exon 2 of 2	NP_859059.1	Q7Z5W3
	BCDIN3D-AS1	NR_027499.1		n.630T>C		non_coding_transcript_exon	Exon 3 of 3
	BCDIN3D-AS1	NR_027501.1		n.626T>C		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCDIN3D	ENST00000333924.6	TSL:1 MANE Select	c.554A>G	p.His185Arg	missense	Exon 2 of 2	ENSP00000335201.4	Q7Z5W3
	BCDIN3D-AS1	ENST00000548872.5	TSL:1	n.631T>C		non_coding_transcript_exon	Exon 3 of 3
	BCDIN3D	ENST00000550861.1	TSL:5	n.1029A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.74
DEOGEN2	Benign	0.00059	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.030	N
PhyloP100		2.5
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.036
Sift	Benign	0.63	T
Sift4G	Benign	0.68	T
Polyphen		0.0010	B
Vest4		0.093
MutPred		0.38		Loss of catalytic residue at W180 (P = 0.1936)
MVP		0.26
MPC		0.16
ClinPred		0.26	T
GERP RS		1.5
Varity_R		0.34
gMVP		0.56
Mutation Taster		=57/43	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: rs1946529422; hg19: chr12-50232479;