Genetic Variant NM_001377960.1:c.2265C>A (chr8-93734146-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001377960.1(RBM12B):c.2265C>A(p.Phe755Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

RBM12B
NM_001377960.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.195

Publications

0 publications found

Variant links:

Genes affected

RBM12B (HGNC:32310): (RNA binding motif protein 12B) Enables RNA binding activity. Predicted to be involved in regulation of RNA splicing. Predicted to be part of ribonucleoprotein complex. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RBM12B links:

ENSG00000253722 (HGNC:):

ENSG00000253722 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06237182).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377960.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBM12B	NM_001377960.1	MANE Select	c.2265C>A	p.Phe755Leu	missense	Exon 4 of 4	NP_001364889.1	Q8IXT5
RBM12B	NM_001377961.1		c.2265C>A	p.Phe755Leu	missense	Exon 5 of 5	NP_001364890.1	Q8IXT5
RBM12B	NM_001377962.1		c.2265C>A	p.Phe755Leu	missense	Exon 3 of 3	NP_001364891.1	Q8IXT5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBM12B	ENST00000520560.6	TSL:2 MANE Select	c.2265C>A	p.Phe755Leu	missense	Exon 4 of 4	ENSP00000429807.2	Q8IXT5
RBM12B	ENST00000517700.6	TSL:1	c.2265C>A	p.Phe755Leu	missense	Exon 3 of 3	ENSP00000427729.2	Q8IXT5
RBM12B	ENST00000399300.7	TSL:2	c.2265C>A	p.Phe755Leu	missense	Exon 3 of 3	ENSP00000382239.2	Q8IXT5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

202330

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.09e-7

AC:

AN:

1410590

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31776

American (AMR)

AF:

0.00

AC:

AN:

37424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22270

East Asian (EAS)

AF:

0.00

AC:

AN:

39332

South Asian (SAS)

AF:

0.00

AC:

AN:

78284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4412

European-Non Finnish (NFE)

AF:

9.19e-7

AC:

AN:

1088308

Other (OTH)

AF:

0.00

AC:

AN:

57806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.2

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.49

M_CAP

Benign

0.0077

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

PhyloP100

-0.20

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.050

REVEL

Benign

0.059

Sift

Uncertain

0.011

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.10

MutPred

0.31

Gain of catalytic residue at F755 (P = 0.0571)

MVP

0.14

ClinPred

0.091

GERP RS

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.13

gMVP

0.13

Mutation Taster

=94/6

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over