Variant 9-122247525-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000417201.4(RBM18):c.320A>T(p.Gln107Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,613,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

RBM18
ENST00000417201.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76

Variant links:

Genes affected

RBM18 (HGNC:28413): (RNA binding motif protein 18) Predicted to enable RNA binding activity. Located in cytosol; intercellular bridge; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RBM18 links:

RBM18 (HGNC:):

RBM18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM18	NM_033117.4 linkuse as main transcript	c.320A>T	p.Gln107Leu	missense_variant	4/6	ENST00000417201.4	NP_149108.1	Q96H35
RBM18	NR_027125.2 linkuse as main transcript	n.462A>T		non_coding_transcript_exon_variant	4/7
RBM18	NR_027126.2 linkuse as main transcript	n.556A>T		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBM18	ENST00000417201.4 linkuse as main transcript	c.320A>T	p.Gln107Leu	missense_variant	4/6	1	NM_033117.4	ENSP00000409315.2	Q96H35
RBM18	ENST00000483428.1 linkuse as main transcript	n.510A>T		non_coding_transcript_exon_variant	5/7	1
RBM18	ENST00000491850.5 linkuse as main transcript	n.22A>T		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251322

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000151

AC:

220

AN:

1461610

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000192

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2022

The c.320A>T (p.Q107L) alteration is located in exon 4 (coding exon 3) of the RBM18 gene. This alteration results from a A to T substitution at nucleotide position 320, causing the glutamine (Q) at amino acid position 107 to be replaced by a leucine (L). 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

Pathogenic

0.78

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Uncertain

0.018

Sift4G

Benign

0.48

Polyphen

0.90

Vest4

0.71

MVP

0.46

MPC

0.43

ClinPred

0.54

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over