Menu
GeneBe

6-88929007-T-G

Variant summary

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

The NM_003800.5(RNGTT):c.345A>C(p.Glu115Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,611,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RNGTT
NM_003800.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00500
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=0.07564005).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNGTTNM_003800.5 linkuse as main transcriptc.345A>C p.Glu115Asp missense_variant 4/16 ENST00000369485.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNGTTENST00000369485.9 linkuse as main transcriptc.345A>C p.Glu115Asp missense_variant 4/161 NM_003800.5 P1O60942-1
RNGTTENST00000369475.7 linkuse as main transcriptc.345A>C p.Glu115Asp missense_variant 4/151 O60942-2
RNGTTENST00000538899.2 linkuse as main transcriptc.345A>C p.Glu115Asp missense_variant 4/121 O60942-3
RNGTTENST00000627296.1 linkuse as main transcriptn.497A>C non_coding_transcript_exon_variant 4/142

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152066
Hom.:
0
Cov.:
32
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
249822
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135048
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000441
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000959
AC:
14
AN:
1459100
Hom.:
0
Cov.:
30
AF XY:
0.00000964
AC XY:
7
AN XY:
725804
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:
0.0000117
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152066
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74272
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4

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 GeneticsJan 29, 2024The c.345A>C (p.E115D) alteration is located in exon 4 (coding exon 4) of the RNGTT gene. This alteration results from a A to C substitution at nucleotide position 345, causing the glutamic acid (E) at amino acid position 115 to be replaced by an aspartic acid (D). 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
0.071
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.63
Cadd
Benign
16
Dann
Uncertain
0.98
DEOGEN2
Benign
0.30
T;.;.
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.43
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.77
T;T;T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.076
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.70
N;N;N
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.86
N;N;.
REVEL
Benign
0.18
Sift
Benign
0.53
T;T;.
Sift4G
Benign
0.62
T;T;T
Polyphen
0.0
B;B;.
Vest4
0.17
MutPred
0.29
Loss of disorder (P = 0.1077);Loss of disorder (P = 0.1077);Loss of disorder (P = 0.1077);
MVP
0.35
MPC
0.53
ClinPred
0.15
T
GERP RS
0.97
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
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: rs747339201; hg19: chr6-89638726; API