Genetic Variant RSRP1:p.Glu224Lys (chr1-25245152-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020317.5(RSRP1):c.670G>A(p.Glu224Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RSRP1
NM_020317.5 missense, splice_region

Scores

Splicing: ADA: 0.00003324

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.583

Publications

0 publications found

Variant links:

Genes affected

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

RSRP1 links:

ENSG00000284657 (HGNC:):

ENSG00000284657 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14829057).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020317.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RSRP1	NM_020317.5	MANE Select	c.670G>A	p.Glu224Lys	missense splice_region	Exon 3 of 5	NP_064713.3
RSRP1	NM_001321772.2		c.670G>A	p.Glu224Lys	missense splice_region	Exon 3 of 5	NP_001308701.1	Q9BUV0-1
RSRP1	NR_135143.2		n.882G>A		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RSRP1	ENST00000431849.3	TSL:1	c.670G>A	p.Glu224Lys	missense	Exon 3 of 3	ENSP00000391510.3	Q9BUV0-2
RSRP1	ENST00000243189.12	TSL:1 MANE Select	c.670G>A	p.Glu224Lys	missense splice_region	Exon 3 of 5	ENSP00000243189.7	Q9BUV0-1
RSRP1	ENST00000568254.5	TSL:1	n.670G>A		splice_region non_coding_transcript_exon	Exon 3 of 5	ENSP00000457195.1	H3BTJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251474

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.000101

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.82

M_CAP

Benign

0.025

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.92

MutationAssessor

Benign

2.0

PhyloP100

0.58

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.036

Sift

Uncertain

0.010

Sift4G

Benign

0.071

Polyphen

0.082

Vest4

0.50

MutPred

0.27

Gain of ubiquitination at E224 (P = 0.0066)

MVP

0.25

MPC

0.053

ClinPred

0.22

GERP RS

2.3

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.27

gMVP

0.42

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.028

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over