12-49838555-T-C

Variant names:

• chr12-49838555-T-C
• rs143226341
• NM_181708.3:c.695A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_181708.3(BCDIN3D):​c.695A>G​(p.Asn232Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000315 in 1,614,162 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: BCDIN3D NM_181708.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0900
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008725256).
• BP6: Variant 12-49838555-T-C is Benign according to our data. Variant chr12-49838555-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3480077.Status of the report is criteria_provided_single_submitter, 1 stars.

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.695A>G	p.Asn232Ser	missense	Exon 2 of 2	NP_859059.1	Q7Z5W3
	BCDIN3D-AS1	NR_027499.1		n.489T>C		non_coding_transcript_exon	Exon 3 of 3
	BCDIN3D-AS1	NR_027500.1		n.485T>C		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCDIN3D	ENST00000333924.6	TSL:1 MANE Select	c.695A>G	p.Asn232Ser	missense	Exon 2 of 2	ENSP00000335201.4	Q7Z5W3
	BCDIN3D-AS1	ENST00000548872.5	TSL:1	n.490T>C		non_coding_transcript_exon	Exon 3 of 3
	BCDIN3D-AS1	ENST00000549124.2	TSL:3	n.475T>C		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000261 AC: 65 AN: 249018 AF XY: 0.000267

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.000350

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000324 AC: 473 AN: 1461890 Hom.: 1 Cov.: 31 AF XY: 0.000336 AC XY: 244 AN XY: 727244

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000487 AC: 26 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000379 AC: 421 AN: 1112010

Other (OTH) AF: 0.000298 AC: 18 AN: 60396

GnomAD4 genome AF: 0.000236 AC: 36 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74470

African (AFR) AF: 0.000144 AC: 6 AN: 41564

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000178 Hom.: 0

Bravo AF: 0.000166

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000272 AC: 33

EpiCase AF: 0.000327

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.054
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.0
DANN	Benign	0.73
DEOGEN2	Benign	0.00045	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.0087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.090
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.020
Sift	Benign	0.66	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.027
MVP		0.12
MPC		0.10
ClinPred		0.0068	T
GERP RS		-2.2
Varity_R		0.064
gMVP		0.27
Mutation Taster		=86/14	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: rs143226341; hg19: chr12-50232338;