6-88801608-C-G

Position:

• chr6-88801608-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003800.5(RNGTT):​c.1294G>C​(p.Glu432Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: RNGTT NM_003800.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.35

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]

ACMG classification

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=0.20446432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNGTT	NM_003800.5	c.1294G>C	p.Glu432Gln	missense_variant	12/16	ENST00000369485.9	NP_003791.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNGTT	ENST00000369485.9	c.1294G>C	p.Glu432Gln	missense_variant	12/16	1	NM_003800.5	ENSP00000358497	P1
RNGTT	ENST00000369475.7	c.1270-31734G>C		intron_variant		1		ENSP00000358487
RNGTT	ENST00000538899.2	c.1270-31734G>C		intron_variant		1		ENSP00000442609
RNGTT	ENST00000627296.1	n.1446G>C		non_coding_transcript_exon_variant	12/14	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2023

The c.1294G>C (p.E432Q) alteration is located in exon 12 (coding exon 12) of the RNGTT gene. This alteration results from a G to C substitution at nucleotide position 1294, causing the glutamic acid (E) at amino acid position 432 to be replaced by a glutamine (Q). 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	0.27
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.59	N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.26
Sift	Benign	0.76	T
Sift4G	Benign	0.77	T
Polyphen		0.0020	B
Vest4		0.32
MutPred		0.57		Gain of methylation at K431 (P = 0.0903);
MVP		0.80
MPC		0.58
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.26
gMVP		0.66

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: chr6-89511327;