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GeneBe

6-88891840-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003800.5(RNGTT):c.760C>G(p.Gln254Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RNGTT
NM_003800.5 missense

Scores

8
9
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.16
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNGTTNM_003800.5 linkuse as main transcriptc.760C>G p.Gln254Glu missense_variant 7/16 ENST00000369485.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNGTTENST00000369485.9 linkuse as main transcriptc.760C>G p.Gln254Glu missense_variant 7/161 NM_003800.5 P1O60942-1
RNGTTENST00000369475.7 linkuse as main transcriptc.760C>G p.Gln254Glu missense_variant 7/151 O60942-2
RNGTTENST00000538899.2 linkuse as main transcriptc.760C>G p.Gln254Glu missense_variant 7/121 O60942-3
RNGTTENST00000627296.1 linkuse as main transcriptn.912C>G non_coding_transcript_exon_variant 7/142

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 GeneticsApr 12, 2022The c.760C>G (p.Q254E) alteration is located in exon 7 (coding exon 7) of the RNGTT gene. This alteration results from a C to G substitution at nucleotide position 760, causing the glutamine (Q) at amino acid position 254 to be replaced by a glutamic acid (E). 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
0.65
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.19
Cadd
Pathogenic
27
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.59
D;.;.
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.87
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.062
D
MetaRNN
Pathogenic
0.81
D;D;D
MetaSVM
Uncertain
0.46
D
MutationAssessor
Uncertain
2.7
M;M;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-2.8
D;D;.
REVEL
Pathogenic
0.68
Sift
Uncertain
0.0030
D;D;.
Sift4G
Uncertain
0.0070
D;D;D
Polyphen
0.99
D;D;.
Vest4
0.80
MutPred
0.46
Loss of ubiquitination at K249 (P = 0.1016);Loss of ubiquitination at K249 (P = 0.1016);Loss of ubiquitination at K249 (P = 0.1016);
MVP
0.85
MPC
1.4
ClinPred
0.96
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.66
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.29
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.29
Position offset: -34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-89601559; API