chr6-88929017-C-T

Variant names:

• chr6-88929017-C-T
• rs142870362
• NM_003800.5:c.335G>A

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.335G>A​(p.Arg112Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,612,040 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R112W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: RNGTT NM_003800.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.94
• Publications: 1 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=0.21590179).

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.335G>A	p.Arg112Gln	missense	Exon 4 of 16	NP_003791.3	O60942-1
	RNGTT	NM_001286426.2		c.335G>A	p.Arg112Gln	missense	Exon 4 of 15	NP_001273355.1	O60942-2
	RNGTT	NM_001286428.2		c.155G>A	p.Arg52Gln	missense	Exon 3 of 14	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.335G>A	p.Arg112Gln	missense	Exon 4 of 16	ENSP00000358497.4	O60942-1
	RNGTT	ENST00000369475.7	TSL:1	c.335G>A	p.Arg112Gln	missense	Exon 4 of 15	ENSP00000358487.4	O60942-2
	RNGTT	ENST00000538899.2	TSL:1	c.335G>A	p.Arg112Gln	missense	Exon 4 of 12	ENSP00000442609.2	O60942-3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151860 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250574 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000336 AC: 49 AN: 1460180 Hom.: 0 Cov.: 30 AF XY: 0.0000358 AC XY: 26 AN XY: 726354

African (AFR) AF: 0.0000299 AC: 1 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39550

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111156

Other (OTH) AF: 0.0000497 AC: 3 AN: 60322

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151860 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74162

African (AFR) AF: 0.0000484 AC: 2 AN: 41354

American (AMR) AF: 0.00 AC: 0 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

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	0.097
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.059
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.59	N
PhyloP100		2.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.22
Sift	Benign	0.28	T
Sift4G	Benign	0.54	T
Polyphen		0.0010	B
Vest4		0.28
MVP		0.68
MPC		0.68
ClinPred		0.10	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.23
Mutation Taster		=73/27	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

dbSNP: rs142870362; hg19: chr6-89638736;