Variant 5-112922129-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000379638.9(REEP5):c.62A>G(p.Asp21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

REEP5
ENST00000379638.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

REEP5 (HGNC:30077): (receptor accessory protein 5) Predicted to be involved in endoplasmic reticulum organization and regulation of intracellular transport. Located in endoplasmic reticulum tubular network. [provided by Alliance of Genome Resources, Apr 2022]

REEP5 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=0.26994556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REEP5	NM_005669.5 linkuse as main transcript	c.62A>G	p.Asp21Gly	missense_variant	1/5	ENST00000379638.9	NP_005660.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP5	ENST00000379638.9 linkuse as main transcript	c.62A>G	p.Asp21Gly	missense_variant	1/5	1	NM_005669.5	ENSP00000368959	P1	Q00765-1
REEP5	ENST00000513339.5 linkuse as main transcript	c.62A>G	p.Asp21Gly	missense_variant	1/4	2		ENSP00000425901
REEP5	ENST00000504247.1 linkuse as main transcript	c.62A>G	p.Asp21Gly	missense_variant	1/3	5		ENSP00000421881
REEP5	ENST00000511865.6 linkuse as main transcript	c.104A>G	p.Asp35Gly	missense_variant, NMD_transcript_variant	1/6	2		ENSP00000421305

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454518

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723586

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.62A>G (p.D21G) alteration is located in exon 1 (coding exon 1) of the REEP5 gene. This alteration results from a A to G substitution at nucleotide position 62, causing the aspartic acid (D) at amino acid position 21 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.40

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.017

D;T;T

Sift4G

Benign

0.13

T;T;D

Polyphen

0.0030

B;P;.

Vest4

0.37

MutPred

0.34

Loss of ubiquitination at K16 (P = 0.046);Loss of ubiquitination at K16 (P = 0.046);Loss of ubiquitination at K16 (P = 0.046);

MVP

0.42

MPC

0.20

ClinPred

0.94

GERP RS

3.1

Varity_R

0.63

gMVP

0.71

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over