6-88844398-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003800.5(RNGTT):c.1228G>A(p.Val410Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 31)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
RNGTT
NM_003800.5 missense
NM_003800.5 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 6.01
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2694373).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNGTT | NM_003800.5 | c.1228G>A | p.Val410Ile | missense_variant | 11/16 | ENST00000369485.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNGTT | ENST00000369485.9 | c.1228G>A | p.Val410Ile | missense_variant | 11/16 | 1 | NM_003800.5 | P1 | |
RNGTT | ENST00000369475.7 | c.1228G>A | p.Val410Ile | missense_variant | 11/15 | 1 | |||
RNGTT | ENST00000538899.2 | c.1228G>A | p.Val410Ile | missense_variant | 11/12 | 1 | |||
RNGTT | ENST00000627296.1 | n.1380G>A | non_coding_transcript_exon_variant | 11/14 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152136Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251004Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135640
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461508Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727034
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152254Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74446
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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 | May 27, 2022 | The c.1228G>A (p.V410I) alteration is located in exon 11 (coding exon 11) of the RNGTT gene. This alteration results from a G to A substitution at nucleotide position 1228, causing the valine (V) at amino acid position 410 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Uncertain
Sift
Benign
T;T;.
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MutPred
Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at