Genetic Variant BCDIN3D:p.Cys202Tyr (chr12-49838645-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_181708.3(BCDIN3D):c.605G>A(p.Cys202Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BCDIN3D
NM_181708.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.71

Publications

0 publications found

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:

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

BCDIN3D-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.898

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCDIN3D	NM_181708.3	MANE Select	c.605G>A	p.Cys202Tyr	missense	Exon 2 of 2	NP_859059.1	Q7Z5W3
BCDIN3D-AS1	NR_027499.1		n.579C>T		non_coding_transcript_exon	Exon 3 of 3
BCDIN3D-AS1	NR_027501.1		n.575C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCDIN3D	ENST00000333924.6	TSL:1 MANE Select	c.605G>A	p.Cys202Tyr	missense	Exon 2 of 2	ENSP00000335201.4	Q7Z5W3
BCDIN3D-AS1	ENST00000548872.5	TSL:1	n.580C>T		non_coding_transcript_exon	Exon 3 of 3
BCDIN3D	ENST00000550861.1	TSL:5	n.1080G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461600

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111766

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.078

MetaRNN

Pathogenic

0.90

MetaSVM

Benign

-0.30

MutationAssessor

Pathogenic

3.1

PhyloP100

7.7

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-9.8

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.88

MutPred

0.73

Loss of helix (P = 0.028)

MVP

0.70

MPC

0.66

ClinPred

1.0

GERP RS

5.3

Varity_R

0.98

gMVP

0.91

Mutation Taster

=11/89

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over