Variant 2-160281360-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016836.4(RBMS1):c.905A>G(p.Gln302Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,098 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RBMS1
NM_016836.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99

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:

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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
RBMS1	NM_016836.4 linkuse as main transcript	c.905A>G	p.Gln302Arg	missense_variant	10/14	ENST00000348849.8
RBMS1	NM_002897.5 linkuse as main transcript	c.896A>G	p.Gln299Arg	missense_variant	10/14
RBMS1	XM_047445368.1 linkuse as main transcript	c.953A>G	p.Gln318Arg	missense_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBMS1	ENST00000348849.8 linkuse as main transcript	c.905A>G	p.Gln302Arg	missense_variant	10/14	1	NM_016836.4	P1	P29558-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456098

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724530

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jan 03, 2024

The c.905A>G (p.Q302R) alteration is located in exon 10 (coding exon 10) of the RBMS1 gene. This alteration results from a A to G substitution at nucleotide position 905, causing the glutamine (Q) at amino acid position 302 to be replaced by an arginine (R). 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

Uncertain

0.38

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;T;T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

T;T;.;.;T

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.49

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.4

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.5

N;N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.29

T;D;T;T;T

Sift4G

Benign

0.34

T;T;T;T;T

Polyphen

0.39

B;.;P;P;P

Vest4

0.88

MVP

0.80

MPC

0.73

ClinPred

0.85

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.89

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