rs6588810

Positions:

• chrX-1634225-G-A

Variant summary

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

The ENST00000381241.9(ASMT):​c.787+935G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,190 control chromosomes in the GnomAD database, including 1,262 homozygotes. There are 8,179 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 0.11 (1262 hom., 8179 hem., cov: 32)
• Consequence: ASMT ENST00000381241.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.787+935G>A		intron_variant		ENST00000381241.9	NP_001164509.1
ASMT	NM_001171039.1	c.563-2213G>A		intron_variant			NP_001164510.1
ASMT	NM_001416525.1	c.703+935G>A		intron_variant			NP_001403454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.787+935G>A		intron_variant		1	NM_001171038.2	ENSP00000370639
ASMT	ENST00000381229.9	c.703+935G>A		intron_variant		1		ENSP00000370627	P1
ASMT	ENST00000381233.8	c.563-2213G>A		intron_variant		1		ENSP00000370631
ASMT	ENST00000509780.6	n.289-2017G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16340 AN: 152072 Hom.: 1264 Cov.: 32 AF XY: 0.110 AC XY: 8176 AN XY: 74266

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.110

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.107 AC: 16335 AN: 152190 Hom.: 1262 Cov.: 32 AF XY: 0.110 AC XY: 8179 AN XY: 74394

Gnomad4 AFR AF: 0.0252

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.111

Bravo AF: 0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.76

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: rs6588810; hg19: chrX-1753118;