rs16983411

Variant names:

• chr21-28877925-A-G
• rs16983411
• NM_013240.6:c.538+267T>C

Variant summary

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

The NM_013240.6(HEMK2):​c.538+267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,126 control chromosomes in the GnomAD database, including 2,352 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 0.17 (2352 hom., cov: 32)
• Consequence: HEMK2 NM_013240.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317
• Publications: 3 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	NM_013240.6	c.538+267T>C		intron_variant	Intron 5 of 5	ENST00000303775.10	NP_037372.4
HEMK2	NM_182749.5	c.454+267T>C		intron_variant	Intron 4 of 4		NP_877426.4
HEMK2	NR_047510.3	n.560+267T>C		intron_variant	Intron 5 of 6
HEMK2	XR_007067787.1	n.560+267T>C		intron_variant	Intron 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
N6AMT1	ENST00000303775.10	c.538+267T>C		intron_variant	Intron 5 of 5	1	NM_013240.6	ENSP00000303584.5
N6AMT1	ENST00000351429.7	c.454+267T>C		intron_variant	Intron 4 of 4	1		ENSP00000286764.4
N6AMT1	ENST00000460212.1	n.538+267T>C		intron_variant	Intron 5 of 6	1		ENSP00000436490.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26163 AN: 152008 Hom.: 2354 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.172 AC: 26167 AN: 152126 Hom.: 2352 Cov.: 32 AF XY: 0.174 AC XY: 12981 AN XY: 74392

African (AFR) AF: 0.164 AC: 6818 AN: 41496

American (AMR) AF: 0.148 AC: 2264 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3468

East Asian (EAS) AF: 0.102 AC: 527 AN: 5174

South Asian (SAS) AF: 0.226 AC: 1092 AN: 4822

European-Finnish (FIN) AF: 0.209 AC: 2211 AN: 10592

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12071 AN: 67982

Other (OTH) AF: 0.194 AC: 409 AN: 2110

Alfa AF: 0.183 Hom.: 352

Bravo AF: 0.162

Asia WGS AF: 0.179 AC: 619 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.8
DANN	Benign	0.44
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs16983411; hg19: chr21-30250247;