rs2232825

Variant names:

• chr1-171794409-C-T
• rs2232825
• NM_015935.5:c.1707C>T
• METTL13 p.Tyr569Tyr

Your query was ambiguous. Multiple possible variants found:

• chr1-171794409-C-T
• chr1-171794409-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_015935.5(METTL13):​c.1707C>T​(p.Tyr569Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,952 control chromosomes in the GnomAD database, including 30,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (2140 hom., cov: 33)
  • Exomes 𝑓: 0.19 (28074 hom.)
• Consequence: METTL13 NM_015935.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.32
• Publications: 22 publications found

Genes affected

METTL13 (HGNC:24248): (methyltransferase 13, eEF1A N-terminus and K55) Predicted to enable methyltransferase activity. Involved in negative regulation of cell cycle G1/S phase transition and negative regulation of transcription by RNA polymerase II. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-171794409-C-T is Benign according to our data. Variant chr1-171794409-C-T is described in ClinVar as Benign. ClinVar VariationId is 3058980.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015935.5. 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
	METTL13	NM_015935.5	MANE Select	c.1707C>T	p.Tyr569Tyr	synonymous	Exon 7 of 8	NP_057019.3
	METTL13	NM_014955.3		c.1449C>T	p.Tyr483Tyr	synonymous	Exon 7 of 8	NP_055770.1	Q8N6R0-3
	METTL13	NM_001007239.2		c.1239C>T	p.Tyr413Tyr	synonymous	Exon 7 of 8	NP_001007240.1	Q8N6R0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL13	ENST00000361735.4	TSL:1 MANE Select	c.1707C>T	p.Tyr569Tyr	synonymous	Exon 7 of 8	ENSP00000354920.3	Q8N6R0-5
	METTL13	ENST00000367737.9	TSL:1	c.1239C>T	p.Tyr413Tyr	synonymous	Exon 7 of 8	ENSP00000356711.5	Q8N6R0-1
	METTL13	ENST00000862970.1		c.1488C>T	p.Tyr496Tyr	synonymous	Exon 6 of 7	ENSP00000533029.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23077 AN: 152110 Hom.: 2140 Cov.: 33

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.167 AC: 41936 AN: 251312 AF XY: 0.168

Gnomad AFR exome AF: 0.0442

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.174

Gnomad EAS exome AF: 0.111

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.191 AC: 279499 AN: 1461724 Hom.: 28074 Cov.: 35 AF XY: 0.189 AC XY: 137597 AN XY: 727168

African (AFR) AF: 0.0440 AC: 1473 AN: 33476

American (AMR) AF: 0.145 AC: 6468 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 4548 AN: 26130

East Asian (EAS) AF: 0.0901 AC: 3575 AN: 39694

South Asian (SAS) AF: 0.111 AC: 9551 AN: 86254

European-Finnish (FIN) AF: 0.206 AC: 10978 AN: 53398

Middle Eastern (MID) AF: 0.139 AC: 799 AN: 5768

European-Non Finnish (NFE) AF: 0.208 AC: 231286 AN: 1111904

Other (OTH) AF: 0.179 AC: 10821 AN: 60390

GnomAD4 genome AF: 0.152 AC: 23064 AN: 152228 Hom.: 2140 Cov.: 33 AF XY: 0.150 AC XY: 11194 AN XY: 74438

African (AFR) AF: 0.0492 AC: 2045 AN: 41550

American (AMR) AF: 0.145 AC: 2222 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3472

East Asian (EAS) AF: 0.110 AC: 570 AN: 5184

South Asian (SAS) AF: 0.103 AC: 498 AN: 4824

European-Finnish (FIN) AF: 0.210 AC: 2225 AN: 10596

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14345 AN: 67990

Other (OTH) AF: 0.153 AC: 322 AN: 2108

Alfa AF: 0.187 Hom.: 6397

Bravo AF: 0.143

Asia WGS AF: 0.105 AC: 364 AN: 3478

EpiCase AF: 0.207

EpiControl AF: 0.201

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	METTL13-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.3
DANN	Benign	0.81
PhyloP100		-2.3
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2232825;

hg19: chr1-171763549;

COSMIC: COSV62282708;

COSMIC: COSV62282708;