rs2756369

Variant names:

• chr6-88616498-C-T
• rs2756369
• NM_003800.5:c.1507-2103G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003800.5(RNGTT):​c.1507-2103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,848 control chromosomes in the GnomAD database, including 7,646 homozygotes. 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: 𝑓 0.27 (7646 hom., cov: 32)
• Consequence: RNGTT NM_003800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNGTT	NM_003800.5	c.1507-2103G>A		intron_variant	Intron 14 of 15	ENST00000369485.9	NP_003791.3
RNGTT	NM_001286426.2	c.1438-2103G>A		intron_variant	Intron 13 of 14		NP_001273355.1
RNGTT	NM_001286428.2	c.1258-2103G>A		intron_variant	Intron 12 of 13		NP_001273357.1
RNGTT	XM_047419443.1	c.1581-2103G>A		intron_variant	Intron 15 of 15		XP_047275399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNGTT	ENST00000369485.9	c.1507-2103G>A		intron_variant	Intron 14 of 15	1	NM_003800.5	ENSP00000358497.4
RNGTT	ENST00000369475.7	c.1438-2103G>A		intron_variant	Intron 13 of 14	1		ENSP00000358487.4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40873 AN: 151732 Hom.: 7631 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.270 AC: 40927 AN: 151848 Hom.: 7646 Cov.: 32 AF XY: 0.266 AC XY: 19739 AN XY: 74220

African (AFR) AF: 0.535 AC: 22140 AN: 41358

American (AMR) AF: 0.229 AC: 3499 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 713 AN: 3472

East Asian (EAS) AF: 0.190 AC: 980 AN: 5160

South Asian (SAS) AF: 0.132 AC: 636 AN: 4814

European-Finnish (FIN) AF: 0.159 AC: 1675 AN: 10526

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10521 AN: 67930

Other (OTH) AF: 0.262 AC: 552 AN: 2108

Alfa AF: 0.214 Hom.: 593

Bravo AF: 0.288

Asia WGS AF: 0.218 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.077
DANN	Benign	0.28
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs2756369; hg19: chr6-89326217;