Variant 1-25246719-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020317.5(RSRP1):c.245C>T(p.Ser82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000423 in 1,607,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

RSRP1
NM_020317.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

Variant links:

Genes affected

RSRP1 (HGNC:25234): (arginine and serine rich protein 1)

RSRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2953357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSRP1	NM_020317.5 linkuse as main transcript	c.245C>T	p.Ser82Leu	missense_variant	2/5	ENST00000243189.12	NP_064713.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSRP1	ENST00000243189.12 linkuse as main transcript	c.245C>T	p.Ser82Leu	missense_variant	2/5	1	NM_020317.5	ENSP00000243189	P1	Q9BUV0-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152256

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000403

AC:

AN:

248386

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

134894

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.0000538

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000440

AC:

AN:

1455204

Hom.:

Cov.:

AF XY:

0.0000457

AC XY:

AN XY:

722572

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:

0.000133

Gnomad4 NFE exome

AF:

0.0000479

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74384

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000330

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

Mar 31, 2024

The c.245C>T (p.S82L) alteration is located in exon 2 (coding exon 1) of the RSRP1 gene. This alteration results from a C to T substitution at nucleotide position 245, causing the serine (S) at amino acid position 82 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

0.84

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

T;.;T;T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.58

T;T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.30

T;T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.9

L;L;.;.;.

MutationTaster

Benign

1.0

D;D;D

PROVEAN

Pathogenic

-4.8

D;D;D;D;D

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D;.;.;.

Sift4G

Uncertain

0.0040

D;D;D;D;.

Polyphen

1.0

D;.;.;.;.

Vest4

0.42

MutPred

0.29

Loss of phosphorylation at S82 (P = 0);Loss of phosphorylation at S82 (P = 0);Loss of phosphorylation at S82 (P = 0);Loss of phosphorylation at S82 (P = 0);Loss of phosphorylation at S82 (P = 0);

MVP

0.54

MPC

0.73

ClinPred

0.62

GERP RS

4.7

Varity_R

0.66

gMVP

0.21

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