rs8134601

Variant names:

• chr21-28807306-G-A
• rs8134601
• ENST00000824773.1:n.100+14599C>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+14599C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,078 control chromosomes in the GnomAD database, including 2,354 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 0.11 (2354 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000824773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.936+14599C>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+14599C>T		intron_variant	Intron 2 of 4
ENSG00000232855	ENST00000824774.1	n.119+14599C>T		intron_variant	Intron 2 of 3
ENSG00000232855	ENST00000824775.1	n.104+14599C>T		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16904 AN: 151960 Hom.: 2347 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00534

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.111 AC: 16937 AN: 152078 Hom.: 2354 Cov.: 32 AF XY: 0.111 AC XY: 8290 AN XY: 74352

African (AFR) AF: 0.324 AC: 13421 AN: 41440

American (AMR) AF: 0.103 AC: 1569 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3466

East Asian (EAS) AF: 0.137 AC: 705 AN: 5160

South Asian (SAS) AF: 0.0411 AC: 198 AN: 4818

European-Finnish (FIN) AF: 0.0297 AC: 315 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00534 AC: 363 AN: 67996

Other (OTH) AF: 0.0791 AC: 167 AN: 2112

Alfa AF: 0.0580 Hom.: 417

Bravo AF: 0.128

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.43
DANN	Benign	0.50
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs8134601; hg19: chr21-30179629;