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GeneBe

6-88612765-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003800.5(RNGTT):c.1748A>G(p.Glu583Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,613,170 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

RNGTT
NM_003800.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48
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]

Genome browser will be placed here

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=0.18398693).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNGTTNM_003800.5 linkuse as main transcriptc.1748A>G p.Glu583Gly missense_variant 16/16 ENST00000369485.9
RNGTTNM_001286426.2 linkuse as main transcriptc.1679A>G p.Glu560Gly missense_variant 15/15
RNGTTNM_001286428.2 linkuse as main transcriptc.1499A>G p.Glu500Gly missense_variant 14/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNGTTENST00000369485.9 linkuse as main transcriptc.1748A>G p.Glu583Gly missense_variant 16/161 NM_003800.5 P1O60942-1
RNGTTENST00000369475.7 linkuse as main transcriptc.1679A>G p.Glu560Gly missense_variant 15/151 O60942-2

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251352
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000260
AC:
38
AN:
1461044
Hom.:
0
Cov.:
32
AF XY:
0.0000248
AC XY:
18
AN XY:
726860
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000324
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152126
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.0000965
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsSep 29, 2023The c.1748A>G (p.E583G) alteration is located in exon 16 (coding exon 16) of the RNGTT gene. This alteration results from a A to G substitution at nucleotide position 1748, causing the glutamic acid (E) at amino acid position 583 to be replaced by a glycine (G). 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
0.18
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.26
Cadd
Uncertain
23
Dann
Uncertain
1.0
DEOGEN2
Benign
0.18
T;.
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.1
N;.
REVEL
Benign
0.16
Sift
Benign
0.23
T;.
Sift4G
Benign
0.23
T;T
Polyphen
0.61
P;P
Vest4
0.29
MVP
0.40
MPC
0.70
ClinPred
0.28
T
GERP RS
5.7
Varity_R
0.17
gMVP
0.41

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.

Other links and lift over

dbSNP: rs764154179; hg19: chr6-89322484; API