rs4933063

Variant names:

• chrX-1636511-C-A
• NM_001171038.2:c.861C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-1636511-C-A
• chrX-1636511-C-G
• chrX-1636511-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001171038.2(ASMT):​c.861C>A​(p.Asp287Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom. 1 hem.)
• Consequence: ASMT NM_001171038.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.861C>A	p.Asp287Glu	missense_variant	Exon 8 of 9	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.777C>A	p.Asp259Glu	missense_variant	Exon 7 of 8		NP_001403454.1
ASMT	NM_001171039.1	c.636C>A	p.Asp212Glu	missense_variant	Exon 6 of 7		NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.861C>A	p.Asp287Glu	missense_variant	Exon 8 of 9	1	NM_001171038.2	ENSP00000370639.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461656 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727134

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0060
DANN	Benign	0.92
DEOGEN2	Benign	0.0094	.;T;.;.
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Pathogenic	0.84	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.6	D;D;N;D
REVEL	Benign	0.17
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.99	D;.;D;.
Vest4		0.35
MutPred		0.86		Gain of methylation at K289 (P = 0.0693);.;.;.;
MVP		0.61
MPC		0.12
ClinPred		0.79	D
GERP RS		1.1
Varity_R		0.35

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: chrX-1755404;