Variant 14-100881065-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001134888.3(RTL1):c.3724C>T(p.Arg1242Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,602,876 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

RTL1
NM_001134888.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.986

Variant links:

Genes affected

RTL1 (HGNC:14665): (retrotransposon Gag like 1) This gene is a retrotransposon-derived, paternally expressed imprinted gene that is highly expressed at the late fetal stage in both the fetus and placenta. It has an overlapping maternally expressed antisense transcript, which contains several microRNAs targeting the transcripts of this gene through an RNA interference (RNAi) mechanism. This gene is essential for maintenance of the fetal capillaries. [provided by RefSeq, Jul 2009]

RTL1 links:

RTL1 (HGNC:):

RTL1 links:

Genome browser will be placed here

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=0.26797602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL1	NM_001134888.3 linkuse as main transcript	c.3724C>T	p.Arg1242Cys	missense_variant	4/4	ENST00000649591.1	NP_001128360.1	A6NKG5B9EK54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RTL1	ENST00000649591.1 linkuse as main transcript	c.3724C>T	p.Arg1242Cys	missense_variant	4/4		NM_001134888.3	ENSP00000497482.1	A6NKG5
MIR431	ENST00000385266.1 linkuse as main transcript	n.59G>A		non_coding_transcript_exon_variant	1/1	6
MIR493HG	ENST00000637474.1 linkuse as main transcript	n.109-8584G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000430

AC:

AN:

232338

Hom.:

AF XY:

0.0000556

AC XY:

AN XY:

125954

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000705

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000387

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000283

AC:

AN:

1450700

Hom.:

Cov.:

AF XY:

0.0000333

AC XY:

AN XY:

720580

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000916

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000356

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000280

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000831

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 15, 2023

The c.3724C>T (p.R1242C) alteration is located in exon 1 (coding exon 1) of the RTL1 gene. This alteration results from a C to T substitution at nucleotide position 3724, causing the arginine (R) at amino acid position 1242 to be replaced by a cysteine (C). 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

0.29

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.72

.;T

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

L;L

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-2.2

.;N

REVEL

Benign

0.21

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

.;D

Vest4

0.70

MutPred

0.48

Loss of disorder (P = 0.0496);Loss of disorder (P = 0.0496);

MVP

0.45

MPC

1.8

ClinPred

0.44

GERP RS

2.5

Varity_R

0.27

gMVP

0.36

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