dbSNP rs10502302: METTL4:n.3008C>T (chr18-2552887-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000573134.1(METTL4):n.3008C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 628,238 control chromosomes in the GnomAD database, including 48,611 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 9795 hom., cov: 32)

Exomes 𝑓: 0.39 ( 38816 hom. )

Consequence

METTL4
ENST00000573134.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.565

Publications

5 publications found

Variant links:

Genes affected

METTL4 (HGNC:24726): (methyltransferase 4, N6-adenosine) Enables RNA methyltransferase activity and site-specific DNA-methyltransferase (adenine-specific) activity. Involved in nucleic acid metabolic process; regulation of RNA metabolic process; and regulation of mitochondrial DNA replication. Located in cytosol; mitochondrial matrix; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

METTL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL4	NM_022840.5 link	c.830-123C>T		intron_variant	Intron 4 of 8	ENST00000574538.2	NP_073751.3	Q8N3J2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
METTL4	ENST00000573134.1 link	n.3008C>T	non_coding_transcript_exon_variant	Exon 3 of 7	1
METTL4	ENST00000574538.2 link	c.830-123C>T	intron_variant	Intron 4 of 8	1	NM_022840.5	ENSP00000458290.1	Q8N3J2
METTL4	ENST00000319888.10 link	c.830-123C>T	intron_variant	Intron 4 of 7	5		ENSP00000320349.6	J3KNJ7
METTL4	ENST00000576251.5 link	c.23-123C>T	intron_variant	Intron 1 of 3	2		ENSP00000460774.1	I3L3W2

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50109

AN:

151866

Hom.:

9786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.324

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.336

GnomAD4 exome

AF:

0.392

AC:

186913

AN:

476254

Hom.:

38816

Cov.:

AF XY:

0.393

AC XY:

100294

AN XY:

255196

show subpopulations

African (AFR)

AF:

0.119

AC:

1522

AN:

12808

American (AMR)

AF:

0.540

AC:

10796

AN:

19994

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

4238

AN:

14696

East Asian (EAS)

AF:

0.620

AC:

19216

AN:

31008

South Asian (SAS)

AF:

0.411

AC:

19344

AN:

47028

European-Finnish (FIN)

AF:

0.414

AC:

13925

AN:

33602

Middle Eastern (MID)

AF:

0.340

AC:

1229

AN:

3620

European-Non Finnish (NFE)

AF:

0.371

AC:

106382

AN:

286484

Other (OTH)

AF:

0.380

AC:

10261

AN:

27014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

5114

10229

15343

20458

25572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

666

1332

1998

2664

3330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.330

AC:

50133

AN:

151984

Hom.:

9795

Cov.:

AF XY:

0.339

AC XY:

25138

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.125

AC:

5191

AN:

41460

American (AMR)

AF:

0.475

AC:

7267

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

1059

AN:

3470

East Asian (EAS)

AF:

0.632

AC:

3277

AN:

5182

South Asian (SAS)

AF:

0.415

AC:

2001

AN:

4820

European-Finnish (FIN)

AF:

0.435

AC:

4579

AN:

10520

Middle Eastern (MID)

AF:

0.305

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.378

AC:

25678

AN:

67932

Other (OTH)

AF:

0.335

AC:

707

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1588

3176

4763

6351

7939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.357

Hom.:

1913

Bravo

AF:

0.329

Asia WGS

AF:

0.473

AC:

1646

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.3

(source)

DANN

Benign

0.53

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over