Variant 1-100274907-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000370128.9(RTCA):c.557G>T(p.Arg186Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000647 in 1,613,406 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 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00067 ( 0 hom. )

Consequence

RTCA
ENST00000370128.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.11

Variant links:

Genes affected

RTCA (HGNC:17981): (RNA 3'-terminal phosphate cyclase) This gene encodes a member of the RNA 3'-phosphate cyclase family. The encoded protein plays a role in RNA metabolism by catalyzing the ATP-dependent conversion of the 3'-phosphate of RNA substrates to a 2',3'-cyclic phosphodiester. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

RTCA 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=0.27585816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTCA	NM_003729.4 linkuse as main transcript	c.557G>T	p.Arg186Leu	missense_variant	6/11	ENST00000370128.9	NP_003720.1
RTCA	NM_001130841.2 linkuse as main transcript	c.596G>T	p.Arg199Leu	missense_variant	7/12		NP_001124313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTCA	ENST00000370128.9 linkuse as main transcript	c.557G>T	p.Arg186Leu	missense_variant	6/11	1	NM_003729.4	ENSP00000359146	P1	O00442-1
RTCA	ENST00000260563.4 linkuse as main transcript	c.596G>T	p.Arg199Leu	missense_variant	7/12	1		ENSP00000260563		O00442-2

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000911

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000294

AC:

AN:

251376

Hom.:

AF XY:

0.000346

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000572

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000668

AC:

976

AN:

1461100

Hom.:

Cov.:

AF XY:

0.000647

AC XY:

470

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000839

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000446

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000911

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000474

Hom.:

Bravo

AF:

0.000408

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000255

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

Mar 20, 2023

The c.596G>T (p.R199L) alteration is located in exon 7 (coding exon 7) of the RTCA gene. This alteration results from a G to T substitution at nucleotide position 596, causing the arginine (R) at amino acid position 199 to be replaced by a leucine (L). 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

Pathogenic

0.63

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

0.0028

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0047

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.25

Sift

Benign

0.35

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.031

B;B

Vest4

0.94

MVP

0.26

MPC

0.15

ClinPred

0.16

GERP RS

4.5

Varity_R

0.35

gMVP

0.92

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