rs1057519427

Positions:

• chr19-1496626-A-AC

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_001329556.3(REEP6):​c.557dupC​(p.Val187fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: REEP6 NM_001329556.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.795

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 Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.123 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-1496626-A-AC is Pathogenic according to our data. Variant chr19-1496626-A-AC is described in ClinVar as [Pathogenic]. Clinvar id is 374991.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REEP6	NM_001329556.3	c.557dupC	p.Val187fs	frameshift_variant	5/6	ENST00000395479.10	NP_001316485.1
REEP6	NM_138393.4	c.517+177dupC		intron_variant		ENST00000233596.8	NP_612402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP6	ENST00000395479.10	c.557dupC	p.Val187fs	frameshift_variant	5/6	3	NM_001329556.3	ENSP00000378861.5
REEP6	ENST00000233596.8	c.517+177dupC		intron_variant		1	NM_138393.4	ENSP00000233596.2
REEP6	ENST00000395484.4	n.341dupC		non_coding_transcript_exon_variant	3/5	5		ENSP00000378865.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 10

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

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

Other links and lift over

dbSNP: rs1057519427; hg19: chr19-1496625;