Variant 6-138907536-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001286611.2(REPS1):c.2281G>A(p.Val761Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

REPS1
NM_001286611.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.54

Variant links:

Genes affected

REPS1 (HGNC:15578): (RALBP1 associated Eps domain containing 1) This gene encodes a signaling adaptor protein with two EH domains that interacts with proteins that participate in signaling, endocytosis and cytoskeletal changes. The encoded protein has been found in association with intersectin 1 and Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 when intersectin 1 was isolated from clathrin-coated pits. The encoded protein has also been shown to interact with amphiphysin, a cytoplasmic protein at the surface of synaptic vesicles. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

REPS1 links:

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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=0.3739445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REPS1	NM_001286611.2 link	c.2281G>A	p.Val761Ile	missense_variant	19/20	ENST00000450536.7	NP_001273540.1	Q96D71-1B2R7D3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REPS1	ENST00000450536.7 link	c.2281G>A	p.Val761Ile	missense_variant	19/20	1	NM_001286611.2	ENSP00000392065.2		Q96D71-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151958

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251414

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135888

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461458

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727042

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:

0.0000116

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151958

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74222

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

T;.;T;.;.;T

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

M_CAP

Benign

0.038

MetaRNN

Benign

0.37

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.0

L;.;.;.;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.69

N;N;N;N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0040

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

D;.;.;D;D;B

Vest4

0.57

MVP

0.30

MPC

0.80

ClinPred

0.86

GERP RS

6.0

Varity_R

0.17

gMVP

0.41

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over