rs1236427

Variant names:

• chr21-28630020-A-C
• rs1236427
• ENST00000433310.6:n.203-3344T>G

Variant summary

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

The ENST00000433310.6(ENSG00000232855):​n.203-3344T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 152,162 control chromosomes in the GnomAD database, including 954 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 0.094 (954 hom., cov: 31)
• Consequence: ENSG00000232855 ENST00000433310.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.937-52640T>G		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000433310.6	n.203-3344T>G		intron_variant	Intron 1 of 4	2
ENSG00000232855	ENST00000824757.1	n.58-3344T>G		intron_variant	Intron 1 of 8
ENSG00000232855	ENST00000824758.1	n.148-3344T>G		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14375 AN: 152042 Hom.: 954 Cov.: 31

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0989

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.0659

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.0945 AC: 14378 AN: 152162 Hom.: 954 Cov.: 31 AF XY: 0.0965 AC XY: 7180 AN XY: 74386

African (AFR) AF: 0.0527 AC: 2188 AN: 41528

American (AMR) AF: 0.178 AC: 2725 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0989 AC: 343 AN: 3468

East Asian (EAS) AF: 0.333 AC: 1720 AN: 5168

South Asian (SAS) AF: 0.0655 AC: 316 AN: 4826

European-Finnish (FIN) AF: 0.0742 AC: 786 AN: 10594

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0877 AC: 5962 AN: 67988

Other (OTH) AF: 0.114 AC: 240 AN: 2110

Alfa AF: 0.0869 Hom.: 170

Bravo AF: 0.106

Asia WGS AF: 0.192 AC: 666 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.92
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs1236427; hg19: chr21-30002342;