Genetic Variant NM_001127395.5:c.-2G>T (chr2-207624377-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001127395.5(METTL21A):c.-2G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,611,738 control chromosomes in the GnomAD database, including 26,940 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 0.23 ( 4893 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22047 hom. )

Consequence

METTL21A
NM_001127395.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0900

Publications

22 publications found

Variant links:

Genes affected

METTL21A (HGNC:30476): (methyltransferase 21A, HSPA lysine) Enables ATPase binding activity; Hsp70 protein binding activity; and protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

METTL21A 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=-0.69).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL21A	NM_001127395.5 link	c.-2G>T		5_prime_UTR_variant	Exon 2 of 4	ENST00000411432.6	NP_001120867.1	Q8WXB1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL21A	ENST00000411432.6 link	c.-2G>T		5_prime_UTR_variant	Exon 2 of 4	2	NM_001127395.5	ENSP00000415115.1		Q8WXB1-1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35183

AN:

151944

Hom.:

4884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.235

GnomAD2 exomes

AF:

0.193

AC:

48026

AN:

248888

AF XY:

0.186

show subpopulations

Gnomad AFR exome

AF:

0.393

Gnomad AMR exome

AF:

0.284

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.168

AC:

245273

AN:

1459676

Hom.:

22047

Cov.:

AF XY:

0.167

AC XY:

120966

AN XY:

726150

show subpopulations

African (AFR)

AF:

0.394

AC:

13132

AN:

33366

American (AMR)

AF:

0.279

AC:

12372

AN:

44350

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

5239

AN:

26058

East Asian (EAS)

AF:

0.178

AC:

7060

AN:

39632

South Asian (SAS)

AF:

0.163

AC:

14045

AN:

86020

European-Finnish (FIN)

AF:

0.140

AC:

7454

AN:

53214

Middle Eastern (MID)

AF:

0.238

AC:

1304

AN:

5480

European-Non Finnish (NFE)

AF:

0.156

AC:

173570

AN:

1111264

Other (OTH)

AF:

0.184

AC:

11097

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

10009

20018

30026

40035

50044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6442

12884

19326

25768

32210

<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:

0.232

AC:

35229

AN:

152062

Hom.:

4893

Cov.:

AF XY:

0.233

AC XY:

17299

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.388

AC:

16069

AN:

41420

American (AMR)

AF:

0.270

AC:

4124

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

745

AN:

3472

East Asian (EAS)

AF:

0.167

AC:

862

AN:

5160

South Asian (SAS)

AF:

0.167

AC:

808

AN:

4826

European-Finnish (FIN)

AF:

0.141

AC:

1495

AN:

10578

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.152

AC:

10337

AN:

68010

Other (OTH)

AF:

0.242

AC:

511

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1321

2642

3962

5283

6604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.198

Hom.:

6148

Bravo

AF:

0.248

Asia WGS

AF:

0.228

AC:

790

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.5

(source)

DANN

Benign

0.83

PhyloP100

0.090

PromoterAI

0.071

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

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