rs1236428

Variant names:

• chr21-28600947-C-T
• rs1236428
• ENST00000430247.1:n.21-23567G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000430247.1(ENSG00000232855):​n.21-23567G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,222 control chromosomes in the GnomAD database, including 55,599 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 0.85 (55599 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000430247.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 0 publications found

Genes affected

ENSG00000232855 (HGNC:58104):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.937-23567G>A		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000430247.1	n.21-23567G>A		intron_variant	Intron 1 of 4	5
ENSG00000232855	ENST00000433310.6	n.295-23567G>A		intron_variant	Intron 2 of 4	2
ENSG00000232855	ENST00000824757.1	n.150-23567G>A		intron_variant	Intron 2 of 8

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129463 AN: 152104 Hom.: 55536 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.842

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.851 AC: 129583 AN: 152222 Hom.: 55599 Cov.: 32 AF XY: 0.852 AC XY: 63445 AN XY: 74436

African (AFR) AF: 0.938 AC: 38972 AN: 41550

American (AMR) AF: 0.883 AC: 13506 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3217 AN: 3470

East Asian (EAS) AF: 0.916 AC: 4743 AN: 5178

South Asian (SAS) AF: 0.837 AC: 4039 AN: 4826

European-Finnish (FIN) AF: 0.778 AC: 8240 AN: 10588

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 54000 AN: 68000

Other (OTH) AF: 0.840 AC: 1774 AN: 2112

Alfa AF: 0.823 Hom.: 28251

Bravo AF: 0.869

Asia WGS AF: 0.844 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.7
DANN	Benign	0.42
PhyloP100		-0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1236428; hg19: chr21-29973269;