Genetic Variant RETREG1:p.Pro29Gln (chr5-16616886-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000306320.10(RETREG1):c.86C>A(p.Pro29Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P29L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RETREG1
ENST00000306320.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Publications

2 publications found

Variant links:

Genes affected

RETREG1 (HGNC:25964): (reticulophagy regulator 1) The protein encoded by this gene is a cis-Golgi transmembrane protein that may be necessary for the long-term survival of nociceptive and autonomic ganglion neurons. Mutations in this gene are a cause of hereditary sensory and autonomic neuropathy type IIB (HSAN IIB), and this gene may also play a role in susceptibility to vascular dementia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

RETREG1 links:

RETREG1-AS1 (HGNC:55551): (RETREG1 antisense RNA 1)

RETREG1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07778618).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000306320.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETREG1	NM_001034850.3	MANE Select	c.86C>A	p.Pro29Gln	missense	Exon 1 of 9	NP_001030022.1
	RETREG1-AS1	NR_109946.1		n.561+400G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RETREG1	ENST00000306320.10	TSL:1 MANE Select	c.86C>A	p.Pro29Gln	missense	Exon 1 of 9	ENSP00000304642.9
RETREG1	ENST00000682229.1		c.86C>A	p.Pro29Gln	missense	Exon 1 of 10	ENSP00000507342.1
RETREG1	ENST00000682564.1		c.86C>A	p.Pro29Gln	missense	Exon 1 of 9	ENSP00000508099.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1332862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

656884

African (AFR)

AF:

0.00

AC:

AN:

26882

American (AMR)

AF:

0.00

AC:

AN:

28812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23574

East Asian (EAS)

AF:

0.00

AC:

AN:

29864

South Asian (SAS)

AF:

0.00

AC:

AN:

74040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1057120

Other (OTH)

AF:

0.00

AC:

AN:

55388

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0053

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.36

M_CAP

Benign

0.0040

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

PhyloP100

1.3

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.27

REVEL

Benign

0.023

Sift

Benign

0.25

Sift4G

Benign

0.15

Polyphen

0.0010

Vest4

0.35

MutPred

0.23

Loss of glycosylation at P29 (P = 9e-04)

MVP

0.12

MPC

0.31

ClinPred

0.068

GERP RS

-0.27

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.031

gMVP

0.19

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over