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GeneBe

6-88941078-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003800.5(RNGTT):c.167G>T(p.Ser56Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RNGTT
NM_003800.5 missense

Scores

3
12
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.34
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNGTTNM_003800.5 linkuse as main transcriptc.167G>T p.Ser56Ile missense_variant 2/16 ENST00000369485.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNGTTENST00000369485.9 linkuse as main transcriptc.167G>T p.Ser56Ile missense_variant 2/161 NM_003800.5 P1O60942-1
RNGTTENST00000369475.7 linkuse as main transcriptc.167G>T p.Ser56Ile missense_variant 2/151 O60942-2
RNGTTENST00000538899.2 linkuse as main transcriptc.167G>T p.Ser56Ile missense_variant 2/121 O60942-3
RNGTTENST00000627296.1 linkuse as main transcriptn.319G>T non_coding_transcript_exon_variant 2/142

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
27
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 GeneticsOct 12, 2021The c.167G>T (p.S56I) alteration is located in exon 2 (coding exon 2) of the RNGTT gene. This alteration results from a G to T substitution at nucleotide position 167, causing the serine (S) at amino acid position 56 to be replaced by an isoleucine (I). 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
0.88
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
Cadd
Pathogenic
29
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.44
T;.;.
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.054
D
MetaRNN
Uncertain
0.57
D;D;D
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.3
M;M;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-3.6
D;D;.
REVEL
Benign
0.25
Sift
Uncertain
0.013
D;D;.
Sift4G
Uncertain
0.036
D;D;T
Polyphen
0.98
D;D;.
Vest4
0.67
MutPred
0.46
Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);
MVP
0.52
MPC
3.4
ClinPred
0.98
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.63
gMVP
0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-89650797; API