rs144198572

Variant names:

• chr21-28885294-C-A
• rs144198572
• NM_013240.6:c.52G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-28885294-C-A
• chr21-28885294-C-G
• chr21-28885294-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013240.6(HEMK2):​c.52G>T​(p.Ala18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 1,438,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A18T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: HEMK2 NM_013240.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 0 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]

ENSG00000307311 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07524243).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013240.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEMK2	NM_013240.6	MANE Select	c.52G>T	p.Ala18Ser	missense	Exon 1 of 6	NP_037372.4	Q9Y5N5-1
	HEMK2	NM_182749.5		c.52G>T	p.Ala18Ser	missense	Exon 1 of 5	NP_877426.4	Q9Y5N5-2
	HEMK2	NR_047510.3		n.74G>T		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEMK2	ENST00000303775.10	TSL:1 MANE Select	c.52G>T	p.Ala18Ser	missense	Exon 1 of 6	ENSP00000303584.5	Q9Y5N5-1
	HEMK2	ENST00000351429.7	TSL:1	c.52G>T	p.Ala18Ser	missense	Exon 1 of 5	ENSP00000286764.4	Q9Y5N5-2
	HEMK2	ENST00000460212.1	TSL:1	n.52G>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000436490.1	Q9Y5N5-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000164 AC: 4 AN: 244154 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000581

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000271

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000417 AC: 6 AN: 1438240 Hom.: 0 Cov.: 38 AF XY: 0.00000281 AC XY: 2 AN XY: 711822

African (AFR) AF: 0.00 AC: 0 AN: 32790

American (AMR) AF: 0.00 AC: 0 AN: 43596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25838

East Asian (EAS) AF: 0.0000785 AC: 3 AN: 38196

South Asian (SAS) AF: 0.00 AC: 0 AN: 85248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1094832

Other (OTH) AF: 0.00 AC: 0 AN: 59158

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.5
DANN	Benign	0.93
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.024
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.82	N
REVEL	Benign	0.020
Sift	Benign	0.41	T
Sift4G	Benign	0.15	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.50		Gain of disorder (P = 0.0187)
MVP		0.13
MPC		0.13
ClinPred		0.033	T
GERP RS		0.20
PromoterAI		-0.0065	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.16
gMVP		0.59
Mutation Taster		=90/10	polymorphism

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: rs144198572; hg19: chr21-30257616;