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GeneBe

1-171782096-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_015935.5(METTL13):c.129T>C(p.His43=) 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 (★).

Frequency

Genomes: 𝑓 0.54 ( 22947 hom., cov: 30)
Exomes 𝑓: 0.47 ( 161899 hom. )

Consequence

METTL13
NM_015935.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.57 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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/exons MANE UniProt
METTL13NM_015935.5 linkuse as main transcriptc.129T>C p.His43= synonymous_variant 1/8 ENST00000361735.4
METTL13NM_001007239.2 linkuse as main transcriptc.129T>C p.His43= synonymous_variant 1/8
METTL13NM_014955.3 linkuse as main transcriptc.-106+301T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
METTL13ENST00000361735.4 linkuse as main transcriptc.129T>C p.His43= synonymous_variant 1/81 NM_015935.5 P1Q8N6R0-5
METTL13ENST00000367737.9 linkuse as main transcriptc.129T>C p.His43= synonymous_variant 1/81 Q8N6R0-1
METTL13ENST00000362019.7 linkuse as main transcriptc.-106+301T>C intron_variant 2 Q8N6R0-3
METTL13ENST00000485629.1 linkuse as main transcriptn.241T>C non_coding_transcript_exon_variant 2/45

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.537
AC:
81466
AN:
151748
Hom.:
22909
Cov.:
30
show subpopulations
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
GnomAD3 exomes
AF:
0.467
AC:
117130
AN:
250784
Hom.:
28837
AF XY:
0.457
AC XY:
61940
AN XY:
135568
show subpopulations
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 SAS exome
AF:
0.313
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
show subpopulations
Gnomad4 AFR exome
AF:
0.718
Gnomad4 AMR exome
AF:
0.397
Gnomad4 ASJ exome
AF:
0.539
Gnomad4 EAS exome
AF:
0.655
Gnomad4 SAS exome
AF:
0.318
Gnomad4 FIN exome
AF:
0.470
Gnomad4 NFE exome
AF:
0.462
Gnomad4 OTH exome
AF:
0.486
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.537
AC:
81554
AN:
151866
Hom.:
22947
Cov.:
30
AF XY:
0.534
AC XY:
39625
AN XY:
74220
show subpopulations
Gnomad4 AFR
AF:
0.708
Gnomad4 AMR
AF:
0.462
Gnomad4 ASJ
AF:
0.523
Gnomad4 EAS
AF:
0.637
Gnomad4 SAS
AF:
0.311
Gnomad4 FIN
AF:
0.482
Gnomad4 NFE
AF:
0.470
Gnomad4 OTH
AF:
0.520
Alfa
AF:
0.480
Hom.:
23982
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

METTL13-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This 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
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2294720; hg19: chr1-171751236; COSMIC: COSV62282702; API