Variant 2-160367366-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1BS2

The ENST00000409075.5(RBMS1):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,324,346 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BS2

High AC in GnomAdExome at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RBMS1	NM_016836.4 linkuse as main transcript	c.101T>C	p.Met34Thr	missense_variant	2/14	ENST00000348849.8
RBMS1	NM_002897.5 linkuse as main transcript	c.101T>C	p.Met34Thr	missense_variant	2/14
RBMS1	XM_047445368.1 linkuse as main transcript	c.101T>C	p.Met34Thr	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>C	p.Met34Thr	missense_variant	2/14	1	NM_016836.4	P1	P29558-1

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

145826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000677

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000243

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000684

AC:

AN:

248706

Hom.:

AF XY:

0.0000891

AC XY:

AN XY:

134632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000360

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000407

AC:

AN:

1178520

Hom.:

Cov.:

AF XY:

0.0000492

AC XY:

AN XY:

589688

show subpopulations

Gnomad4 AFR exome

AF:

0.0000371

Gnomad4 AMR exome

AF:

0.000101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000409

Gnomad4 SAS exome

AF:

0.000159

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000874

GnomAD4 genome

AF:

0.0000137

AC:

AN:

145826

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

71080

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000677

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000243

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000659

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

Sep 01, 2021

The c.101T>C (p.M34T) alteration is located in exon 2 (coding exon 2) of the RBMS1 gene. This alteration results from a T to C substitution at nucleotide position 101, causing the methionine (M) at amino acid position 34 to be replaced by a threonine (T). 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

0.55

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Uncertain

0.090

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.34

T;T;T;T;T;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;.;.;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.35

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

M;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.7

D;.;D;D;D;D

REVEL

Benign

0.27

Sift

Benign

0.046

D;.;D;D;D;D

Sift4G

Benign

0.17

T;T;D;D;D;.

Polyphen

0.44

B;.;B;B;B;B

Vest4

0.70

MVP

0.50

MPC

0.57

ClinPred

0.23

GERP RS

5.6

Varity_R

0.44

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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