dbSNP rs1997605: HEMK2:c.134+116C>T (chr21-28885096-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 NM_013240.6(HEMK2):c.134+116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 1,371,842 control chromosomes in the GnomAD database, including 516,835 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 0.81 ( 50284 hom., cov: 31)

Exomes 𝑓: 0.87 ( 466551 hom. )

Consequence

HEMK2
NM_013240.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.748

Publications

11 publications found

Variant links:

Genes affected

HEMK2 (HGNC:16021): (N-6 adenine-specific DNA methyltransferase 1) This gene encodes an N(6)-adenine-specific DNA methyltransferase. The encoded enzyme may be involved in the methylation of release factor I during translation termination. This enzyme is also involved in converting the arsenic metabolite monomethylarsonous acid to the less toxic dimethylarsonic acid. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Mar 2023]

HEMK2 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=-0.72).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013240.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HEMK2	NM_013240.6	MANE Select	c.134+116C>T	intron	N/A	NP_037372.4
HEMK2	NM_182749.5		c.134+116C>T	intron	N/A	NP_877426.4
HEMK2	NR_047510.3		n.156+116C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
N6AMT1	ENST00000303775.10	TSL:1 MANE Select	c.134+116C>T	intron	N/A	ENSP00000303584.5
N6AMT1	ENST00000351429.7	TSL:1	c.134+116C>T	intron	N/A	ENSP00000286764.4
N6AMT1	ENST00000460212.1	TSL:1	n.134+116C>T	intron	N/A	ENSP00000436490.1

Frequencies

GnomAD3 genomes

AF:

0.807

AC:

122584

AN:

151968

Hom.:

50262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.886

Gnomad AMR

AF:

0.766

Gnomad ASJ

AF:

0.881

Gnomad EAS

AF:

0.510

Gnomad SAS

AF:

0.926

Gnomad FIN

AF:

0.909

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.878

Gnomad OTH

AF:

0.819

GnomAD4 exome

AF:

0.871

AC:

1062092

AN:

1219756

Hom.:

466551

AF XY:

0.873

AC XY:

518985

AN XY:

594484

show subpopulations

African (AFR)

AF:

0.685

AC:

17789

AN:

25984

American (AMR)

AF:

0.709

AC:

14758

AN:

20824

Ashkenazi Jewish (ASJ)

AF:

0.884

AC:

15012

AN:

16976

East Asian (EAS)

AF:

0.469

AC:

15010

AN:

32012

South Asian (SAS)

AF:

0.943

AC:

49224

AN:

52180

European-Finnish (FIN)

AF:

0.917

AC:

35850

AN:

39116

Middle Eastern (MID)

AF:

0.830

AC:

3996

AN:

4812

European-Non Finnish (NFE)

AF:

0.887

AC:

867657

AN:

978294

Other (OTH)

AF:

0.864

AC:

42796

AN:

49558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

6326

12652

18977

25303

31629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20336

40672

61008

81344

101680

<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:

0.807

AC:

122661

AN:

152086

Hom.:

50284

Cov.:

AF XY:

0.807

AC XY:

60054

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.692

AC:

28682

AN:

41442

American (AMR)

AF:

0.765

AC:

11706

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.881

AC:

3058

AN:

3470

East Asian (EAS)

AF:

0.510

AC:

2623

AN:

5144

South Asian (SAS)

AF:

0.926

AC:

4464

AN:

4820

European-Finnish (FIN)

AF:

0.909

AC:

9639

AN:

10602

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.878

AC:

59718

AN:

67994

Other (OTH)

AF:

0.818

AC:

1729

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1142

2284

3426

4568

5710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<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:

0.862

Hom.:

29029

Bravo

AF:

0.784

Asia WGS

AF:

0.727

AC:

2531

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.6

(source)

DANN

Benign

0.87

PhyloP100

0.75

PromoterAI

-0.0059

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over