X-1630017-T-C

Position:

• chrX-1630017-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001171038.2(ASMT):​c.562+78T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,277,486 control chromosomes in the GnomAD database, including 15,282 homozygotes. There are 97,639 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1553 hom., 10212 hem., cov: 32)
  • Exomes 𝑓: 0.15 (13729 hom. 87427 hem.)
• Consequence: ASMT NM_001171038.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

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]

ASMT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.562+78T>C		intron_variant		ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.562+78T>C		intron_variant			NP_001403454.1
ASMT	NM_001171039.1	c.562+78T>C		intron_variant			NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.562+78T>C		intron_variant		1	NM_001171038.2	ENSP00000370639.3
ASMT	ENST00000381229.9	c.562+78T>C		intron_variant		1		ENSP00000370627.4
ASMT	ENST00000381233.8	c.562+78T>C		intron_variant		1		ENSP00000370631.3
ASMT	ENST00000509780.6	n.288+1984T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20432 AN: 151812 Hom.: 1552 Cov.: 32 AF XY: 0.138 AC XY: 10203 AN XY: 74120

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.150 AC: 168712 AN: 1125556 Hom.: 13729 AF XY: 0.152 AC XY: 87427 AN XY: 573548

Gnomad4 AFR exome AF: 0.0878

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.364

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.135 AC: 20436 AN: 151930 Hom.: 1553 Cov.: 32 AF XY: 0.138 AC XY: 10212 AN XY: 74248

Gnomad4 AFR AF: 0.0838

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.150

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.15

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: rs28675287; hg19: chrX-1748910; COSMIC: COSV67110026;