dbSNP rs1057519317: REEP6:p.Pro128Leu (chr19-1496319-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5

The NM_001329556.3(REEP6):c.383C>T(p.Pro128Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P128A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

REEP6
NM_001329556.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.50

Publications

4 publications found

Variant links:

Genes affected

REEP6 (HGNC:30078): (receptor accessory protein 6) The protein encoded by this gene may be involved in the transport of receptors from the endoplasmic reticulum (ER) to the cell surface. The encoded protein may also play a role in regulating ER membrane structure. This gene is required for the proper development of retinal rods and photoreceptors, with defects in this gene being associated with retinitis pigmentosa 77. [provided by RefSeq, May 2017]

REEP6 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
retinitis pigmentosa 77
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

REEP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 19-1496319-C-T is Pathogenic according to our data. Variant chr19-1496319-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 374992.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP6	NM_001329556.3 link	c.383C>T	p.Pro128Leu	missense_variant	Exon 4 of 6	ENST00000395479.10	NP_001316485.1
REEP6	NM_138393.4 link	c.383C>T	p.Pro128Leu	missense_variant	Exon 4 of 5	ENST00000233596.8	NP_612402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
REEP6	ENST00000395479.10 link	c.383C>T	p.Pro128Leu	missense_variant	Exon 4 of 6	3	NM_001329556.3	ENSP00000378861.5	Q96HR9-1
REEP6	ENST00000233596.8 link	c.383C>T	p.Pro128Leu	missense_variant	Exon 4 of 5	1	NM_138393.4	ENSP00000233596.2	Q96HR9-2
REEP6	ENST00000395484.4 link	n.167C>T		non_coding_transcript_exon_variant	Exon 2 of 5	5		ENSP00000378865.4	A8MXN1
REEP6	ENST00000591735.2 link	n.*138C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

249588

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459516

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725886

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111252

Other (OTH)

AF:

0.00

AC:

AN:

60332

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Retinitis pigmentosa 77

Pathogenic:1

Jan 19, 2017

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.30

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

0.036

MutationAssessor

Benign

1.6

PhyloP100

4.5

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.56

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.035

Vest4

0.51

MutPred

0.58

Gain of MoRF binding (P = 0.0587);

MVP

0.93

MPC

0.26

ClinPred

0.91

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.38

Mutation Taster

=37/63

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over