Variant chr17-42582143-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_178126.4(RETREG3):c.1071G>A(p.Met357Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RETREG3
NM_178126.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.340

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:

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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=0.0637438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RETREG3	NM_178126.4 linkuse as main transcript	c.1071G>A	p.Met357Ile	missense_variant	9/9	ENST00000309428.10	NP_835227.1	Q86VR2-1
RETREG3	XM_047435503.1 linkuse as main transcript	c.780G>A	p.Met260Ile	missense_variant	10/10		XP_047291459.1
RETREG3	NR_026697.2 linkuse as main transcript	n.1143G>A		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.1071G>A	p.Met357Ile	missense_variant	9/9	1	NM_178126.4	ENSP00000309432.4		Q86VR2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251300

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Oct 07, 2024

The c.1071G>A (p.M357I) alteration is located in exon 9 (coding exon 9) of the FAM134C gene. This alteration results from a G to A substitution at nucleotide position 1071, causing the methionine (M) at amino acid position 357 to be replaced by an isoleucine (I). 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

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.48

N;.

REVEL

Benign

0.032

Sift

Benign

0.14

T;.

Sift4G

Benign

0.44

T;T

Polyphen

0.0

B;.

Vest4

0.068

MutPred

0.32

Gain of catalytic residue at M357 (P = 0.0051);.;

MVP

0.24

MPC

0.15

ClinPred

0.030

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.043

gMVP

0.072

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