X-1615250-C-G

Variant names:

• chrX-1615250-C-G
• rs17149149
• NM_001171038.2:c.51C>G

Variant summary

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

The NM_001171038.2(ASMT):​c.51C>G​(p.Asn17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ASMT NM_001171038.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• Publications: 0 publications found

Genes affected

ASMT (HGNC:750): (acetylserotonin O-methyltransferase) This gene belongs to the methyltransferase superfamily, and is located in the pseudoautosomal region (PAR) at the end of the short arms of the X and Y chromosomes. The encoded enzyme catalyzes the final reaction in the synthesis of melatonin, and is abundant in the pineal gland. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171038.2. 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
	ASMT	NM_001171038.2	MANE Select	c.51C>G	p.Asn17Lys	missense	Exon 1 of 9	NP_001164509.1	P46597-3
	ASMT	NM_001416525.1		c.51C>G	p.Asn17Lys	missense	Exon 1 of 8	NP_001403454.1	X5D2A4
	ASMT	NM_001171039.1		c.51C>G	p.Asn17Lys	missense	Exon 1 of 7	NP_001164510.1	X5D784

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASMT	ENST00000381241.9	TSL:1 MANE Select	c.51C>G	p.Asn17Lys	missense	Exon 1 of 9	ENSP00000370639.3	P46597-3
	ASMT	ENST00000381229.9	TSL:1	c.51C>G	p.Asn17Lys	missense	Exon 1 of 8	ENSP00000370627.4	P46597-1
	ASMT	ENST00000381233.8	TSL:1	c.51C>G	p.Asn17Lys	missense	Exon 1 of 7	ENSP00000370631.3	P46597-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 219496 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.0
DANN	Benign	0.97
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.86
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.15
Sift	Benign	0.044	D
Sift4G	Uncertain	0.057	T
Polyphen		0.99	D
Vest4		0.23
MutPred		0.86		Gain of ubiquitination at N17 (P = 0.0388)
MVP		0.43
MPC		0.10
ClinPred		0.97	D
GERP RS		-2.3
PromoterAI		-0.046	Neutral
Varity_R		0.32
Mutation Taster		=86/14	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: rs17149149; hg19: chrX-1734143;