chr1-171782096-T-C

Variant names:

• chr1-171782096-T-C
• rs2294720
• NM_015935.5:c.129T>C

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.129T>C​(p.His43His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,613,446 control chromosomes in the GnomAD database, including 184,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.54 (22947 hom., cov: 30)
  • Exomes 𝑓: 0.47 (161899 hom.)
• Consequence: METTL13 NM_015935.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.57
• Publications: 21 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=-0.61).
• BP6: Variant 1-171782096-T-C is Benign according to our data. Variant chr1-171782096-T-C is described in ClinVar as [Benign]. Clinvar id is 3059095.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL13	NM_015935.5	c.129T>C	p.His43His	synonymous_variant	Exon 1 of 8	ENST00000361735.4	NP_057019.3
METTL13	NM_001007239.2	c.129T>C	p.His43His	synonymous_variant	Exon 1 of 8		NP_001007240.1
METTL13	NM_014955.3	c.-106+301T>C		intron_variant	Intron 1 of 7		NP_055770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL13	ENST00000361735.4	c.129T>C	p.His43His	synonymous_variant	Exon 1 of 8	1	NM_015935.5	ENSP00000354920.3
METTL13	ENST00000367737.9	c.129T>C	p.His43His	synonymous_variant	Exon 1 of 8	1		ENSP00000356711.5
METTL13	ENST00000485629.1	n.241T>C		non_coding_transcript_exon_variant	Exon 2 of 4	5
METTL13	ENST00000362019.7	c.-106+301T>C		intron_variant	Intron 1 of 7	2		ENSP00000355393.3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81466 AN: 151748 Hom.: 22909 Cov.: 30

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.519

GnomAD2 exomes AF: 0.467 AC: 117130 AN: 250784 AF XY: 0.457

Gnomad AFR exome AF: 0.705

Gnomad AMR exome AF: 0.391

Gnomad ASJ exome AF: 0.547

Gnomad EAS exome AF: 0.640

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.462

Gnomad OTH exome AF: 0.471

GnomAD4 exome AF: 0.465 AC: 680319 AN: 1461580 Hom.: 161899 Cov.: 42 AF XY: 0.461 AC XY: 334950 AN XY: 727098

African (AFR) AF: 0.718 AC: 24042 AN: 33472

American (AMR) AF: 0.397 AC: 17750 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 14078 AN: 26128

East Asian (EAS) AF: 0.655 AC: 25988 AN: 39694

South Asian (SAS) AF: 0.318 AC: 27447 AN: 86246

European-Finnish (FIN) AF: 0.470 AC: 25097 AN: 53402

Middle Eastern (MID) AF: 0.459 AC: 2640 AN: 5756

European-Non Finnish (NFE) AF: 0.462 AC: 513913 AN: 1111796

Other (OTH) AF: 0.486 AC: 29364 AN: 60384

GnomAD4 genome AF: 0.537 AC: 81554 AN: 151866 Hom.: 22947 Cov.: 30 AF XY: 0.534 AC XY: 39625 AN XY: 74220

African (AFR) AF: 0.708 AC: 29307 AN: 41388

American (AMR) AF: 0.462 AC: 7062 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1816 AN: 3470

East Asian (EAS) AF: 0.637 AC: 3280 AN: 5146

South Asian (SAS) AF: 0.311 AC: 1499 AN: 4820

European-Finnish (FIN) AF: 0.482 AC: 5077 AN: 10534

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.470 AC: 31902 AN: 67928

Other (OTH) AF: 0.520 AC: 1097 AN: 2110

Alfa AF: 0.488 Hom.: 32971

Bravo AF: 0.542

Asia WGS AF: 0.509 AC: 1772 AN: 3478

EpiCase AF: 0.455

EpiControl AF: 0.456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

METTL13-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		1.6
PromoterAI		0.076	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=98/2	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: rs2294720; hg19: chr1-171751236; COSMIC: COSV62282702;