NM_001122965.1:c.2258G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001122965.1(RPTN):​c.2258G>A​(p.Ser753Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RPTN
NM_001122965.1 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.182
Variant links:
Genes affected
RPTN (HGNC:26809): (repetin) Predicted to enable calcium ion binding activity and transition metal ion binding activity. Predicted to be located in cytosol. Predicted to be active in cornified envelope. [provided by Alliance of Genome Resources, Apr 2022]
PUDPP2 (HGNC:20195): (pseudouridine 5'-phosphatase pseudogene 2)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.025613397).
BP6
Variant 1-152154841-C-T is Benign according to our data. Variant chr1-152154841-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2536986.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPTNNM_001122965.1 linkc.2258G>A p.Ser753Asn missense_variant Exon 3 of 3 ENST00000316073.3 NP_001116437.1 Q6XPR3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPTNENST00000316073.3 linkc.2258G>A p.Ser753Asn missense_variant Exon 3 of 3 1 NM_001122965.1 ENSP00000317895.3 Q6XPR3
PUDPP2ENST00000628080.1 linkn.48-30136G>A intron_variant Intron 1 of 1 5

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
151470
Hom.:
0
Cov.:
32
FAILED QC
Gnomad AFR
AF:
0.0000243
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.84e-7
AC:
1
AN:
1461620
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727114
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000660
AC:
1
AN:
151586
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74080
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000590
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Apr 13, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.010
DANN
Benign
0.13
DEOGEN2
Benign
0.0040
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0040
N
LIST_S2
Benign
0.11
T
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.026
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-1.6
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.29
N
REVEL
Benign
0.015
Sift
Benign
0.87
T
Sift4G
Benign
0.74
T
Polyphen
0.0
B
Vest4
0.035
MVP
0.13
MPC
0.021
ClinPred
0.051
T
GERP RS
-5.5
Varity_R
0.029
gMVP
0.0041

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.

Other links and lift over

dbSNP: rs867204909; hg19: chr1-152127317; API