Variant chr14-100883371-C-G 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.1418G>C(p.Trp473Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,776 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: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

RTL1
NM_001134888.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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:

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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=0.2408844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL1	NM_001134888.3 linkuse as main transcript	c.1418G>C	p.Trp473Ser	missense_variant	4/4	ENST00000649591.1	NP_001128360.1
RTL1	XM_047431358.1 linkuse as main transcript	c.1418G>C	p.Trp473Ser	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.1418G>C	p.Trp473Ser	missense_variant	4/4		NM_001134888.3	ENSP00000497482	P1
MIR493HG	ENST00000699458.1 linkuse as main transcript	n.315C>G		non_coding_transcript_exon_variant	1/6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1398776

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689778

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 14, 2023

The c.1418G>C (p.W473S) alteration is located in exon 1 (coding exon 1) of the RTL1 gene. This alteration results from a G to C substitution at nucleotide position 1418, causing the tryptophan (W) at amino acid position 473 to be replaced by a serine (S). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.0034

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.10

T;T

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.47

.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

0.94

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.7

.;N

REVEL

Benign

0.18

Sift

Benign

0.74

.;T

Sift4G

Pathogenic

0.0

.;D

Vest4

0.65

MutPred

0.46

Gain of catalytic residue at N469 (P = 0);Gain of catalytic residue at N469 (P = 0);

MVP

0.33

MPC

1.8

ClinPred

0.71

GERP RS

4.1

Varity_R

0.18

gMVP

0.57

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over