Variant chr14-100883659-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001134888.3(RTL1):c.1130G>A(p.Arg377Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,551,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

RTL1
NM_001134888.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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:

MIR493HG (HGNC:55978): (MIR493 cluster host gene)

MIR493HG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.090171784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL1	NM_001134888.3 linkuse as main transcript	c.1130G>A	p.Arg377Gln	missense_variant	4/4	ENST00000649591.1	NP_001128360.1
RTL1	XM_047431358.1 linkuse as main transcript	c.1130G>A	p.Arg377Gln	missense_variant	3/3		XP_047287314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTL1	ENST00000649591.1 linkuse as main transcript	c.1130G>A	p.Arg377Gln	missense_variant	4/4		NM_001134888.3	ENSP00000497482	P1
MIR493HG	ENST00000699458.1 linkuse as main transcript	n.603C>T		non_coding_transcript_exon_variant	1/6

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00318

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000325

AC:

AN:

153812

Hom.:

AF XY:

0.0000490

AC XY:

AN XY:

81644

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000336

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000643

AC:

AN:

1399250

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

690130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000769

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000526

AC:

AN:

151992

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000773

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000755

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

Aug 28, 2023

The c.1130G>A (p.R377Q) alteration is located in exon 1 (coding exon 1) of the RTL1 gene. This alteration results from a G to A substitution at nucleotide position 1130, causing the arginine (R) at amino acid position 377 to be replaced by a glutamine (Q). 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

-0.28

BayesDel_noAF

Benign

-0.51

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.090

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.76

.;N

REVEL

Benign

0.071

Sift

Benign

0.15

.;T

Sift4G

Pathogenic

0.0

.;D

Vest4

0.31

MVP

0.072

MPC

1.5

ClinPred

0.33

GERP RS

3.5

Varity_R

0.073

gMVP

0.30

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