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GeneBe

6-88844418-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.1208A>G(p.Lys403Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 1,614,128 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 0.00029 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

RNGTT
NM_003800.5 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90
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=0.20090526).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNGTTNM_003800.5 linkuse as main transcriptc.1208A>G p.Lys403Arg missense_variant 11/16 ENST00000369485.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNGTTENST00000369485.9 linkuse as main transcriptc.1208A>G p.Lys403Arg missense_variant 11/161 NM_003800.5 P1O60942-1
RNGTTENST00000369475.7 linkuse as main transcriptc.1208A>G p.Lys403Arg missense_variant 11/151 O60942-2
RNGTTENST00000538899.2 linkuse as main transcriptc.1208A>G p.Lys403Arg missense_variant 11/121 O60942-3
RNGTTENST00000627296.1 linkuse as main transcriptn.1360A>G non_coding_transcript_exon_variant 11/142

Frequencies

GnomAD3 genomes
AF:
0.000282
AC:
43
AN:
152226
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.000529
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000251
AC:
63
AN:
251302
Hom.:
0
AF XY:
0.000295
AC XY:
40
AN XY:
135818
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000260
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:
0.000449
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000247
AC:
361
AN:
1461784
Hom.:
0
Cov.:
31
AF XY:
0.000238
AC XY:
173
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000201
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:
0.000301
Gnomad4 OTH exome
AF:
0.000265
GnomAD4 genome
AF:
0.000289
AC:
44
AN:
152344
Hom.:
0
Cov.:
31
AF XY:
0.000282
AC XY:
21
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000529
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000362
Hom.:
0
Bravo
AF:
0.000268
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000280
AC:
34
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000600
EpiControl
AF:
0.000593

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 GeneticsDec 19, 2022The c.1208A>G (p.K403R) alteration is located in exon 11 (coding exon 11) of the RNGTT gene. This alteration results from a A to G substitution at nucleotide position 1208, causing the lysine (K) at amino acid position 403 to be replaced by an arginine (R). 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
0.091
BayesDel_addAF
Benign
-0.042
T
BayesDel_noAF
Uncertain
0.030
Cadd
Benign
21
Dann
Uncertain
0.99
DEOGEN2
Benign
0.11
T;.;.
Eigen
Benign
-0.12
Eigen_PC
Benign
0.12
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.20
T;T;T
MetaSVM
Benign
-0.69
T
MutationAssessor
Benign
1.2
L;L;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.94
N;N;.
REVEL
Uncertain
0.36
Sift
Benign
0.49
T;T;.
Sift4G
Benign
0.78
T;T;T
Polyphen
0.053
B;B;.
Vest4
0.64
MVP
0.91
MPC
0.53
ClinPred
0.053
T
GERP RS
5.8
Varity_R
0.17
gMVP
0.51

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: rs201214592; hg19: chr6-89554137; API