rs1057519317

Positions:

• chr19-1496319-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.50

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 374992.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-1496319-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REEP6	NM_001329556.3	c.383C>T	p.Pro128Leu	missense_variant	4/6	ENST00000395479.10
REEP6	NM_138393.4	c.383C>T	p.Pro128Leu	missense_variant	4/5	ENST00000233596.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REEP6	ENST00000395479.10	c.383C>T	p.Pro128Leu	missense_variant	4/6	3	NM_001329556.3
REEP6	ENST00000233596.8	c.383C>T	p.Pro128Leu	missense_variant	4/5	1	NM_138393.4	P1
REEP6	ENST00000395484.4	c.167C>T	p.Pro56Leu	missense_variant, NMD_transcript_variant	2/5	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459516 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725886

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa 77 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 19, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	26
DANN	Uncertain	0.99
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	0.036	D
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.035	D
Vest4		0.51
MutPred		0.58		Gain of MoRF binding (P = 0.0587);
MVP		0.93
MPC		0.26
ClinPred		0.91	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.38

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

LitVar

Other links and lift over

dbSNP: rs1057519317; hg19: chr19-1496318;