6-88881919-C-A

Variant names:

• chr6-88881919-C-A
• rs13209883
• NM_003800.5:c.896+8576G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003800.5(RNGTT):​c.896+8576G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 152,316 control chromosomes in the GnomAD database, including 80 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 0.028 (80 hom., cov: 32)
• Consequence: RNGTT NM_003800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0281 (4282/152316) while in subpopulation NFE AF = 0.0418 (2841/68018). AF 95% confidence interval is 0.0405. There are 80 homozygotes in GnomAd4. There are 2004 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 80 gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNGTT	NM_003800.5	MANE Select	c.896+8576G>T		intron	N/A	NP_003791.3
	RNGTT	NM_001286426.2		c.896+8576G>T		intron	N/A	NP_001273355.1
	RNGTT	NM_001286428.2		c.716+8576G>T		intron	N/A	NP_001273357.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNGTT	ENST00000369485.9	TSL:1 MANE Select	c.896+8576G>T		intron	N/A	ENSP00000358497.4
	RNGTT	ENST00000369475.7	TSL:1	c.896+8576G>T		intron	N/A	ENSP00000358487.4
	RNGTT	ENST00000538899.2	TSL:1	c.896+8576G>T		intron	N/A	ENSP00000442609.2

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4284 AN: 152198 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0281 AC: 4282 AN: 152316 Hom.: 80 Cov.: 32 AF XY: 0.0269 AC XY: 2004 AN XY: 74496

African (AFR) AF: 0.00856 AC: 356 AN: 41566

American (AMR) AF: 0.0261 AC: 399 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.0230 AC: 111 AN: 4824

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10622

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0418 AC: 2841 AN: 68018

Other (OTH) AF: 0.0388 AC: 82 AN: 2116

Alfa AF: 0.0351 Hom.: 74

Bravo AF: 0.0293

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-0.39
Mutation Taster		=100/0	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: rs13209883; hg19: chr6-89591638;