dbSNP rs1048546: HEMK2:c.*3830C>A (chr21-28872555-G-T) – 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.*3830C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,008 control chromosomes in the GnomAD database, including 8,710 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 ( 8709 hom., cov: 32)

Exomes 𝑓: 0.40 ( 1 hom. )

Consequence

HEMK2
NM_013240.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.629

Publications

20 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (Cadd=0.741).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 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	UniProt
HEMK2	NM_013240.6	MANE Select	c.*3830C>A	3_prime_UTR	Exon 6 of 6	NP_037372.4	Q9Y5N5-1
HEMK2	NM_182749.5		c.*3830C>A	3_prime_UTR	Exon 5 of 5	NP_877426.4	Q9Y5N5-2
HEMK2	NR_047510.3		n.925C>A	non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HEMK2	ENST00000303775.10	TSL:1 MANE Select	c.*3830C>A	3_prime_UTR	Exon 6 of 6	ENSP00000303584.5	Q9Y5N5-1
HEMK2	ENST00000351429.7	TSL:1	c.*3830C>A	3_prime_UTR	Exon 5 of 5	ENSP00000286764.4	Q9Y5N5-2
HEMK2	ENST00000460212.1	TSL:1	n.*258C>A	non_coding_transcript_exon	Exon 7 of 7	ENSP00000436490.1	Q9Y5N5-1

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50693

AN:

151870

Hom.:

8700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.355

GnomAD4 exome

AF:

0.400

AC:

AN:

Hom.:

Cov.:

AF XY:

0.313

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.429

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.334

AC:

50729

AN:

151988

Hom.:

8709

Cov.:

AF XY:

0.336

AC XY:

24935

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.362

AC:

14988

AN:

41444

American (AMR)

AF:

0.374

AC:

5707

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

988

AN:

3468

East Asian (EAS)

AF:

0.593

AC:

3064

AN:

5166

South Asian (SAS)

AF:

0.300

AC:

1446

AN:

4816

European-Finnish (FIN)

AF:

0.299

AC:

3162

AN:

10558

Middle Eastern (MID)

AF:

0.356

AC:

104

AN:

292

European-Non Finnish (NFE)

AF:

0.299

AC:

20304

AN:

67954

Other (OTH)

AF:

0.354

AC:

745

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1742

3483

5225

6966

8708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.313

Hom.:

32133

Bravo

AF:

0.342

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

CADD

Benign

0.74

(source)

PhyloP100

-0.63

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over