chr2-138002119-G-T

Variant names:

• chr2-138002119-G-T
• NM_006895.3:c.354G>T

Variant summary

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

The NM_006895.3(HNMT):​c.354G>T​(p.Glu118Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,376 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: 6.9e-7 (0 hom.)
• Consequence: HNMT NM_006895.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

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.354G>T	p.Glu118Asp	missense_variant	Exon 4 of 6	ENST00000280097.5	NP_008826.1
HNMT	XM_017003948.2	c.252G>T	p.Glu84Asp	missense_variant	Exon 4 of 6		XP_016859437.1
HNMT	XM_017003949.3	c.354G>T	p.Glu118Asp	missense_variant	Exon 4 of 5		XP_016859438.1
HNMT	XM_011511064.3	c.-25G>T		5_prime_UTR_variant	Exon 3 of 5		XP_011509366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNMT	ENST00000280097.5	c.354G>T	p.Glu118Asp	missense_variant	Exon 4 of 6	1	NM_006895.3	ENSP00000280097.3
HNMT	ENST00000410115.5	c.354G>T	p.Glu118Asp	missense_variant	Exon 5 of 7	5		ENSP00000386940.1
HNMT	ENST00000467390.5	n.366G>T		non_coding_transcript_exon_variant	Exon 4 of 5	2
HNMT	ENST00000485653.1	n.286G>T		non_coding_transcript_exon_variant	Exon 3 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451376 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 722044

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: 9.04e-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	0.51
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.0090	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.093
Sift	Benign	0.062	T;T
Sift4G	Benign	0.086	T;T
Polyphen		0.93	P;P
Vest4		0.61
MutPred		0.28		Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);
MVP		0.32
MPC		0.24
ClinPred		0.95	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.57

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: chr2-138759689;