rs16983303

Variant names:

• chr21-28790253-C-A
• rs16983303
• ENST00000824773.1:n.100+31652G>T

Variant summary

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

The ENST00000824773.1(ENSG00000232855):​n.100+31652G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,018 control chromosomes in the GnomAD database, including 5,401 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 0.21 (5401 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000824773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778
• Publications: 2 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.936+31652G>T		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000824773.1	n.100+31652G>T		intron_variant	Intron 2 of 4
ENSG00000232855	ENST00000824774.1	n.119+31652G>T		intron_variant	Intron 2 of 3
ENSG00000232855	ENST00000824775.1	n.104+31652G>T		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31447 AN: 151900 Hom.: 5378 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0769

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0765

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.207 AC: 31518 AN: 152018 Hom.: 5401 Cov.: 32 AF XY: 0.208 AC XY: 15424 AN XY: 74320

African (AFR) AF: 0.458 AC: 18966 AN: 41424

American (AMR) AF: 0.188 AC: 2871 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1906 AN: 5170

South Asian (SAS) AF: 0.130 AC: 626 AN: 4816

European-Finnish (FIN) AF: 0.0769 AC: 813 AN: 10566

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0765 AC: 5199 AN: 67982

Other (OTH) AF: 0.164 AC: 345 AN: 2110

Alfa AF: 0.139 Hom.: 691

Bravo AF: 0.228

Asia WGS AF: 0.237 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.7
DANN	Benign	0.48
PhyloP100		0.78

Splicing

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

Other links and lift over

dbSNP: rs16983303; hg19: chr21-30162575;