Variant 14-100880953-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001134888.3(RTL1):c.3836G>A(p.Arg1279His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0031 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0010 ( 0 hom. )

Consequence

RTL1
NM_001134888.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.53

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033262968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL1	NM_001134888.3 linkuse as main transcript	c.3836G>A	p.Arg1279His	missense_variant	4/4	ENST00000649591.1	NP_001128360.1
RTL1	XM_047431358.1 linkuse as main transcript	c.3836G>A	p.Arg1279His	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.3836G>A	p.Arg1279His	missense_variant	4/4		NM_001134888.3	ENSP00000497482	P1

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

AN:

1282

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0417

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00108

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000138

AC:

AN:

43424

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

23928

show subpopulations

Gnomad AFR exome

AF:

0.000442

Gnomad AMR exome

AF:

0.000707

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000383

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00112

GnomAD4 exome

AF:

0.00101

AC:

AN:

43494

Hom.:

Cov.:

AF XY:

0.000677

AC XY:

AN XY:

25114

show subpopulations

Gnomad4 AFR exome

AF:

0.00966

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00269

Gnomad4 SAS exome

AF:

0.000718

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.00363

GnomAD4 genome

AF:

0.00312

AC:

AN:

1282

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

AN XY:

794

show subpopulations

Gnomad4 AFR

AF:

0.0167

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0417

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00108

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000100

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

Feb 10, 2022

The c.3836G>A (p.R1279H) 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 3836, causing the arginine (R) at amino acid position 1279 to be replaced by a histidine (H). 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

0.096

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.098

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.53

.;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.72

.;N

REVEL

Benign

0.031

Sift

Benign

0.030

.;D

Sift4G

Uncertain

0.055

.;T

Vest4

0.062

MutPred

0.27

Gain of catalytic residue at P1277 (P = 8e-04);Gain of catalytic residue at P1277 (P = 8e-04);

MVP

0.048

MPC

1.0

ClinPred

0.037

GERP RS

-2.3

Varity_R

0.035

gMVP

0.085

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