rs17650204

Variant names:

• chr1-171785931-A-G
• rs17650204
• NM_015935.5:c.966A>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.966A>G​(p.Lys322Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 1,613,564 control chromosomes in the GnomAD database, including 7,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.072 (556 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6816 hom.)
• Consequence: METTL13 NM_015935.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.26
• Publications: 12 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=-0.47).
• BP6: Variant 1-171785931-A-G is Benign according to our data. Variant chr1-171785931-A-G is described in ClinVar as Benign. ClinVar VariationId is 3055433.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=3.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 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.966A>G	p.Lys322Lys	synonymous	Exon 3 of 8	NP_057019.3
	METTL13	NM_014955.3		c.708A>G	p.Lys236Lys	synonymous	Exon 3 of 8	NP_055770.1	Q8N6R0-3
	METTL13	NM_001007239.2		c.498A>G	p.Lys166Lys	synonymous	Exon 3 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.966A>G	p.Lys322Lys	synonymous	Exon 3 of 8	ENSP00000354920.3	Q8N6R0-5
	METTL13	ENST00000367737.9	TSL:1	c.498A>G	p.Lys166Lys	synonymous	Exon 3 of 8	ENSP00000356711.5	Q8N6R0-1
	METTL13	ENST00000862970.1		c.966A>G	p.Lys322Lys	synonymous	Exon 3 of 7	ENSP00000533029.1

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10903 AN: 152068 Hom.: 556 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0966

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0272

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0665

GnomAD2 exomes AF: 0.0750 AC: 18791 AN: 250640 AF XY: 0.0761

Gnomad AFR exome AF: 0.0139

Gnomad AMR exome AF: 0.0371

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.0824

GnomAD4 exome AF: 0.0915 AC: 133722 AN: 1461378 Hom.: 6816 Cov.: 31 AF XY: 0.0906 AC XY: 65879 AN XY: 726948

African (AFR) AF: 0.0130 AC: 435 AN: 33472

American (AMR) AF: 0.0387 AC: 1729 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2695 AN: 26122

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39696

South Asian (SAS) AF: 0.0310 AC: 2671 AN: 86208

European-Finnish (FIN) AF: 0.118 AC: 6301 AN: 53402

Middle Eastern (MID) AF: 0.0662 AC: 367 AN: 5540

European-Non Finnish (NFE) AF: 0.103 AC: 114414 AN: 1111876

Other (OTH) AF: 0.0845 AC: 5102 AN: 60354

GnomAD4 genome AF: 0.0716 AC: 10904 AN: 152186 Hom.: 556 Cov.: 32 AF XY: 0.0708 AC XY: 5267 AN XY: 74390

African (AFR) AF: 0.0164 AC: 680 AN: 41528

American (AMR) AF: 0.0554 AC: 847 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0966 AC: 335 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0272 AC: 131 AN: 4820

European-Finnish (FIN) AF: 0.117 AC: 1241 AN: 10594

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7424 AN: 67996

Other (OTH) AF: 0.0658 AC: 139 AN: 2112

Alfa AF: 0.0932 Hom.: 2547

Bravo AF: 0.0635

Asia WGS AF: 0.0180 AC: 63 AN: 3478

EpiCase AF: 0.107

EpiControl AF: 0.102

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	-0.47
CADD	Benign	10
DANN	Benign	0.62
PhyloP100		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17650204; hg19: chr1-171755071;