Variant 6-88801569-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003800.5(RNGTT):c.1333A>G(p.Thr445Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,458,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

RNGTT
NM_003800.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.491

Variant links:

Genes affected

RNGTT (HGNC:10073): (RNA guanylyltransferase and 5'-phosphatase) Enables mRNA guanylyltransferase activity and triphosphatase activity. Involved in 7-methylguanosine mRNA capping. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RNGTT links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048994035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNGTT	NM_003800.5 linkuse as main transcript	c.1333A>G	p.Thr445Ala	missense_variant	12/16	ENST00000369485.9	NP_003791.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNGTT	ENST00000369485.9 linkuse as main transcript	c.1333A>G	p.Thr445Ala	missense_variant	12/16	1	NM_003800.5	ENSP00000358497	P1	O60942-1
RNGTT	ENST00000369475.7 linkuse as main transcript	c.1270-31695A>G		intron_variant		1		ENSP00000358487		O60942-2
RNGTT	ENST00000538899.2 linkuse as main transcript	c.1270-31695A>G		intron_variant		1		ENSP00000442609		O60942-3
RNGTT	ENST00000627296.1 linkuse as main transcript	n.1485A>G		non_coding_transcript_exon_variant	12/14	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1458602

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725700

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:

0.00000901

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

Oct 03, 2023

The c.1333A>G (p.T445A) alteration is located in exon 12 (coding exon 12) of the RNGTT gene. This alteration results from a A to G substitution at nucleotide position 1333, causing the threonine (T) at amino acid position 445 to be replaced by an alanine (A). 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

0.064

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.1

DANN

Benign

0.37

DEOGEN2

Benign

0.082

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.028

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.012

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.72

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

0.37

REVEL

Benign

0.16

Sift

Benign

0.78

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.22

MVP

0.38

MPC

0.58

ClinPred

0.013

GERP RS

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

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

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