Variant chr2-160367366-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1

The ENST00000409075.5(RBMS1):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0097 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RBMS1
ENST00000409075.5 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Variant links:

Genes affected

RBMS1 (HGNC:9907): (RNA binding motif single stranded interacting protein 1) This gene encodes a member of a small family of proteins which bind single stranded DNA/RNA. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. These proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. Several transcript variants, resulting from alternative splicing and encoding different isoforms, have been described. A pseudogene for this locus is found on chromosome 12. [provided by RefSeq, Feb 2009]

RBMS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Start lost variant, no new inframe start found.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RBMS1	NM_016836.4 linkuse as main transcript	c.101T>A	p.Met34Lys	missense_variant	2/14	ENST00000348849.8
RBMS1	NM_002897.5 linkuse as main transcript	c.101T>A	p.Met34Lys	missense_variant	2/14
RBMS1	XM_047445368.1 linkuse as main transcript	c.101T>A	p.Met34Lys	missense_variant	2/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBMS1	ENST00000348849.8 linkuse as main transcript	c.101T>A	p.Met34Lys	missense_variant	2/14	1	NM_016836.4	P1	P29558-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

113

AN:

145740

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000743

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00102

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00476

Gnomad SAS

AF:

0.00535

Gnomad FIN

AF:

0.00107

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000227

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00965

AC:

11262

AN:

1166634

Hom.:

Cov.:

AF XY:

0.00962

AC XY:

5616

AN XY:

583664

show subpopulations

Gnomad4 AFR exome

AF:

0.0173

Gnomad4 AMR exome

AF:

0.00926

Gnomad4 ASJ exome

AF:

0.0261

Gnomad4 EAS exome

AF:

0.0319

Gnomad4 SAS exome

AF:

0.00216

Gnomad4 FIN exome

AF:

0.0147

Gnomad4 NFE exome

AF:

0.00850

Gnomad4 OTH exome

AF:

0.0186

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000782

AC:

114

AN:

145868

Hom.:

Cov.:

AF XY:

0.000801

AC XY:

AN XY:

71140

show subpopulations

Gnomad4 AFR

AF:

0.000791

Gnomad4 AMR

AF:

0.00102

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00476

Gnomad4 SAS

AF:

0.00510

Gnomad4 FIN

AF:

0.00107

Gnomad4 NFE

AF:

0.000227

Gnomad4 OTH

AF:

0.00

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

Mar 31, 2022

The c.101T>A (p.M34K) alteration is located in exon 2 (coding exon 2) of the RBMS1 gene. This alteration results from a T to A substitution at nucleotide position 101, causing the methionine (M) at amino acid position 34 to be replaced by a lysine (K). 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

0.71

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.50

D;T;T;T;T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;.;.;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.55

D;D;D;D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.8

M;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.2

D;.;D;D;D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.028

D;.;D;D;D;D

Sift4G

Benign

0.18

T;T;D;D;D;.

Polyphen

0.44

B;.;B;B;B;P

Vest4

0.72

MutPred

0.41

Gain of solvent accessibility (P = 4e-04);.;.;.;.;.;

MVP

0.47

MPC

0.76

ClinPred

0.95

GERP RS

5.6

Varity_R

0.69

gMVP

0.78

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