Genetic Variant RPTN:p.Gly645Ser (chr1-152155166-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001122965.1(RPTN):c.1933G>A(p.Gly645Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

RPTN
NM_001122965.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.133

Publications

2 publications found

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]

RPTN links:

ENSG00000293250 (HGNC:):

ENSG00000293250 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027958602).

BP6

Variant 1-152155166-C-T is Benign according to our data. Variant chr1-152155166-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3156301.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122965.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTN	NM_001122965.1	MANE Select	c.1933G>A	p.Gly645Ser	missense	Exon 3 of 3	NP_001116437.1	Q6XPR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTN	ENST00000316073.3	TSL:1 MANE Select	c.1933G>A	p.Gly645Ser	missense	Exon 3 of 3	ENSP00000317895.3	Q6XPR3
	ENSG00000293250	ENST00000628080.1	TSL:5	n.48-30461G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000104

AC:

AN:

249138

AF XY:

0.0000886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000797

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.0000739

AC:

108

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000839

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.000179

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000773

AC:

AN:

1112012

Other (OTH)

AF:

0.000116

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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

AF:

0.0000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000581

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.056

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.24

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.0025

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00036

LIST_S2

Benign

0.32

M_CAP

Benign

0.0014

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.35

PhyloP100

-0.13

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.39

REVEL

Benign

0.021

Sift

Benign

0.59

Sift4G

Benign

0.81

Polyphen

0.0030

Vest4

0.019

MVP

0.11

MPC

0.021

ClinPred

0.0073

GERP RS

-2.8

Varity_R

0.036

gMVP

0.044

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over