6-88904876-G-T

Variant names:

• chr6-88904876-G-T
• rs781008784
• NM_003800.5:c.523C>A

Variant summary

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

The NM_003800.5(RNGTT):​c.523C>A​(p.Arg175Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNGTT NM_003800.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNGTT	NM_003800.5	c.523C>A	p.Arg175Ser	missense_variant	Exon 6 of 16	ENST00000369485.9	NP_003791.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNGTT	ENST00000369485.9	c.523C>A	p.Arg175Ser	missense_variant	Exon 6 of 16	1	NM_003800.5	ENSP00000358497.4
RNGTT	ENST00000369475.7	c.523C>A	p.Arg175Ser	missense_variant	Exon 6 of 15	1		ENSP00000358487.4
RNGTT	ENST00000538899.2	c.523C>A	p.Arg175Ser	missense_variant	Exon 6 of 12	1		ENSP00000442609.2
RNGTT	ENST00000627296.1	n.675C>A		non_coding_transcript_exon_variant	Exon 6 of 14	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.;.
Eigen	Benign	-0.0046
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.99	L;L;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.7	D;D;.
REVEL	Benign	0.13
Sift	Benign	0.16	T;T;.
Sift4G	Benign	0.35	T;T;T
Polyphen		0.018	B;B;.
Vest4		0.44
MutPred		0.51		Gain of glycosylation at R175 (P = 0.0219);Gain of glycosylation at R175 (P = 0.0219);Gain of glycosylation at R175 (P = 0.0219);
MVP		0.38
MPC		0.69
ClinPred		0.80	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: -49

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs781008784; hg19: chr6-89614595;