X-1615250-C-G

Position:

• chrX-1615250-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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 same amino acid change has been previously reported as Likely benignin UniProt.

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

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

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/exons	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.51C>G	p.Asn17Lys	missense_variant	1/9	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.51C>G	p.Asn17Lys	missense_variant	1/8		NP_001403454.1
ASMT	NM_001171039.1	c.51C>G	p.Asn17Lys	missense_variant	1/7		NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.51C>G	p.Asn17Lys	missense_variant	1/9	1	NM_001171038.2	ENSP00000370639
ASMT	ENST00000381229.9	c.51C>G	p.Asn17Lys	missense_variant	1/8	1		ENSP00000370627	P1
ASMT	ENST00000381233.8	c.51C>G	p.Asn17Lys	missense_variant	1/7	1		ENSP00000370631

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.8	M;M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.15
Sift	Benign	0.044	D;T;T
Sift4G	Uncertain	0.057	T;T;T
Polyphen		0.99	D;.;D
Vest4		0.23
MutPred		0.86		Gain of ubiquitination at N17 (P = 0.0388);Gain of ubiquitination at N17 (P = 0.0388);Gain of ubiquitination at N17 (P = 0.0388);
MVP		0.43
MPC		0.10
ClinPred		0.97	D
GERP RS		-2.3
Varity_R		0.32

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

LitVar

Other links and lift over

dbSNP: rs17149149; hg19: chrX-1734143;