Variant 17-42582114-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000309428.10(RETREG3):c.1100C>G(p.Pro367Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000214 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

RETREG3
ENST00000309428.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

Variant links:

Genes affected

RETREG3 (HGNC:27258): (reticulophagy regulator family member 3) Involved in positive regulation of neuron projection development. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RETREG3 links:

RETREG3 (HGNC:):

RETREG3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06357843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RETREG3	NM_178126.4 linkuse as main transcript	c.1100C>G	p.Pro367Arg	missense_variant	9/9	ENST00000309428.10	NP_835227.1	Q86VR2-1
RETREG3	XM_047435503.1 linkuse as main transcript	c.809C>G	p.Pro270Arg	missense_variant	10/10		XP_047291459.1
RETREG3	NR_026697.2 linkuse as main transcript	n.1172C>G		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RETREG3	ENST00000309428.10 linkuse as main transcript	c.1100C>G	p.Pro367Arg	missense_variant	9/9	1	NM_178126.4	ENSP00000309432.4		Q86VR2-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000167

AC:

AN:

251078

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000222

AC:

324

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

155

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

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:

0.000276

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000145

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000325

Hom.:

Bravo

AF:

0.000166

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000474

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

Aug 30, 2021

The c.1100C>G (p.P367R) alteration is located in exon 9 (coding exon 9) of the FAM134C gene. This alteration results from a C to G substitution at nucleotide position 1100, causing the proline (P) at amino acid position 367 to be replaced by an arginine (R). 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

0.068

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.068

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.25

N;.

REVEL

Benign

0.065

Sift

Benign

0.54

T;.

Sift4G

Benign

0.52

T;T

Polyphen

0.14

B;.

Vest4

0.098

MVP

0.65

MPC

0.16

ClinPred

0.043

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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