Variant 19-12734639-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 ENST00000242784.5(TRIR):c.19C>T(p.Arg7Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 1,510,220 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

TRIR
ENST00000242784.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

Variant links:

Genes affected

TRIR (HGNC:28424): (telomerase RNA component interacting RNase) Enables 3'-5' exonuclease activity and 5'-3' exonuclease activity. Involved in RNA phosphodiester bond hydrolysis, exonucleolytic and rRNA catabolic process. [provided by Alliance of Genome Resources, Apr 2022]

TRIR 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=0.29309005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIR	NM_024038.4 linkuse as main transcript	c.19C>T	p.Arg7Trp	missense_variant	1/3	ENST00000242784.5	NP_076943.1
TRIR	NM_001329738.2 linkuse as main transcript	c.19C>T	p.Arg7Trp	missense_variant	1/2		NP_001316667.1
TRIR	NM_001329739.2 linkuse as main transcript	c.19C>T	p.Arg7Trp	missense_variant	1/3		NP_001316668.1
TRIR	NR_138095.2 linkuse as main transcript	n.46C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TRIR	ENST00000242784.5 linkuse as main transcript	c.19C>T	p.Arg7Trp	missense_variant	1/3	1	NM_024038.4	ENSP00000242784	P3
TRIR	ENST00000592273.5 linkuse as main transcript	c.19C>T	p.Arg7Trp	missense_variant	1/2	3		ENSP00000466801
TRIR	ENST00000588213.1 linkuse as main transcript	c.19C>T	p.Arg7Trp	missense_variant	1/3	3		ENSP00000466196	A1
TRIR	ENST00000591254.1 linkuse as main transcript	c.19C>T	p.Arg7Trp	missense_variant, NMD_transcript_variant	1/3	2		ENSP00000468415

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152052

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.36e-7

AC:

AN:

1358168

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

669884

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:

9.36e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74268

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:

0.0000147

Gnomad4 OTH

AF:

0.00

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

Jul 13, 2021

The c.19C>T (p.R7W) alteration is located in exon 1 (coding exon 1) of the C19orf43 gene. This alteration results from a C to T substitution at nucleotide position 19, causing the arginine (R) at amino acid position 7 to be replaced by a tryptophan (W). 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

0.76

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.024

T;T;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

D;D;D

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.44

MutationTaster

Benign

0.92

D;D;D

PROVEAN

Benign

-1.6

.;N;.

REVEL

Benign

0.21

Sift

Pathogenic

0.0

.;D;.

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.30

MutPred

0.29

Loss of methylation at R7 (P = 0.0229);Loss of methylation at R7 (P = 0.0229);Loss of methylation at R7 (P = 0.0229);

MVP

0.47

MPC

2.6

ClinPred

0.96

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.20

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