chr6-88801608-C-G

Variant names:

• chr6-88801608-C-G
• NM_003800.5:c.1294G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20446432).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003800.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNGTT	NM_003800.5	MANE Select	c.1294G>C	p.Glu432Gln	missense	Exon 12 of 16	NP_003791.3	O60942-1
	RNGTT	NM_001286426.2		c.1270-31734G>C		intron	N/A	NP_001273355.1	O60942-2
	RNGTT	NM_001286428.2		c.1090-31734G>C		intron	N/A	NP_001273357.1	B4DSJ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNGTT	ENST00000369485.9	TSL:1 MANE Select	c.1294G>C	p.Glu432Gln	missense	Exon 12 of 16	ENSP00000358497.4	O60942-1
	RNGTT	ENST00000369475.7	TSL:1	c.1270-31734G>C		intron	N/A	ENSP00000358487.4	O60942-2
	RNGTT	ENST00000538899.2	TSL:1	c.1270-31734G>C		intron	N/A	ENSP00000442609.2	O60942-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.3
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
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

hg19: chr6-89511327;