rs115462439

Variant names:

• chr18-13746277-C-T
• rs115462439
• NM_003799.3:c.1197C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_003799.3(RNMT):​c.1197C>T​(p.Tyr399Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,574,236 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (37 hom.)
• Consequence: RNMT NM_003799.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.47
• Publications: 4 publications found

Genes affected

RNMT (HGNC:10075): (RNA guanine-7 methyltransferase) Enables RNA binding activity and mRNA (guanine-N7-)-methyltransferase activity. Involved in 7-methylguanosine mRNA capping. Located in fibrillar center and nucleoplasm. Part of mRNA cap binding activity complex; mRNA cap methyltransferase complex; and receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 18-13746277-C-T is Benign according to our data. Variant chr18-13746277-C-T is described in ClinVar as Benign. ClinVar VariationId is 773596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.47 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003799.3. 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
	RNMT	NM_003799.3	MANE Select	c.1197C>T	p.Tyr399Tyr	synonymous	Exon 9 of 12	NP_003790.1	O43148-1
	RNMT	NM_001308263.2		c.1197C>T	p.Tyr399Tyr	synonymous	Exon 9 of 12	NP_001295192.1	O43148-2
	RNMT	NM_001378134.1		c.1197C>T	p.Tyr399Tyr	synonymous	Exon 8 of 11	NP_001365063.1	O43148-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNMT	ENST00000383314.7	TSL:1 MANE Select	c.1197C>T	p.Tyr399Tyr	synonymous	Exon 9 of 12	ENSP00000372804.2	O43148-1
	RNMT	ENST00000543302.6	TSL:1	c.1197C>T	p.Tyr399Tyr	synonymous	Exon 8 of 11	ENSP00000446426.1	O43148-1
	RNMT	ENST00000589866.5	TSL:1	c.1197C>T	p.Tyr399Tyr	synonymous	Exon 8 of 11	ENSP00000466252.1	O43148-1

Frequencies

GnomAD3 genomes AF: 0.00514 AC: 781 AN: 152006 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000991

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00578

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00888

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00522 AC: 1246 AN: 238522 AF XY: 0.00515

Gnomad AFR exome AF: 0.00127

Gnomad AMR exome AF: 0.00128

Gnomad ASJ exome AF: 0.00250

Gnomad EAS exome AF: 0.00225

Gnomad FIN exome AF: 0.00564

Gnomad NFE exome AF: 0.00838

Gnomad OTH exome AF: 0.00414

GnomAD4 exome AF: 0.00659 AC: 9373 AN: 1422112 Hom.: 37 Cov.: 27 AF XY: 0.00647 AC XY: 4593 AN XY: 709484

African (AFR) AF: 0.00145 AC: 46 AN: 31738

American (AMR) AF: 0.00151 AC: 60 AN: 39750

Ashkenazi Jewish (ASJ) AF: 0.00242 AC: 62 AN: 25606

East Asian (EAS) AF: 0.00194 AC: 76 AN: 39226

South Asian (SAS) AF: 0.00191 AC: 160 AN: 83690

European-Finnish (FIN) AF: 0.00595 AC: 317 AN: 53260

Middle Eastern (MID) AF: 0.00211 AC: 12 AN: 5684

European-Non Finnish (NFE) AF: 0.00768 AC: 8323 AN: 1084130

Other (OTH) AF: 0.00537 AC: 317 AN: 59028

GnomAD4 genome AF: 0.00513 AC: 781 AN: 152124 Hom.: 4 Cov.: 33 AF XY: 0.00473 AC XY: 352 AN XY: 74352

African (AFR) AF: 0.000988 AC: 41 AN: 41486

American (AMR) AF: 0.00150 AC: 23 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5178

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.00578 AC: 61 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00888 AC: 604 AN: 67998

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00796 Hom.: 2

Bravo AF: 0.00507

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.45
PhyloP100		2.5
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
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: rs115462439; hg19: chr18-13746276;