NM_006895.3:c.107T>A

Variant names:

• chr2-137964598-T-A
• NM_006895.3:c.107T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006895.3(HNMT):​c.107T>A​(p.Met36Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HNMT NM_006895.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66

Genes affected

HNMT (HGNC:5028): (histamine N-methyltransferase) In mammals, histamine is metabolized by two major pathways: N(tau)-methylation via histamine N-methyltransferase and oxidative deamination via diamine oxidase. This gene encodes the first enzyme which is found in the cytosol and uses S-adenosyl-L-methionine as the methyl donor. In the mammalian brain, the neurotransmitter activity of histamine is controlled by N(tau)-methylation as diamine oxidase is not found in the central nervous system. A common genetic polymorphism affects the activity levels of this gene product in red blood cells. Multiple alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNMT	NM_006895.3	c.107T>A	p.Met36Lys	missense_variant	Exon 1 of 6	ENST00000280097.5	NP_008826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNMT	ENST00000280097.5	c.107T>A	p.Met36Lys	missense_variant	Exon 1 of 6	1	NM_006895.3	ENSP00000280097.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461596 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727114

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T;.;T;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	.;T;T;.
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M;M;M;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.2	N;D;N;D
REVEL	Benign	0.14
Sift	Uncertain	0.019	D;D;D;D
Sift4G	Uncertain	0.021	D;D;D;D
Polyphen		0.10	B;P;B;.
Vest4		0.61
MutPred		0.61		Loss of stability (P = 0.0125);Loss of stability (P = 0.0125);Loss of stability (P = 0.0125);Loss of stability (P = 0.0125);
MVP		0.64
MPC		0.14
ClinPred		0.93	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.79

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-138722168;