X-1632831-C-T

Position:

• chrX-1632831-C-T

Variant summary

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

The NM_001171038.2(ASMT):​c.646+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 479,862 control chromosomes in the GnomAD database, including 9,099 homozygotes. There are 47,759 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 0.19 (2589 hom., 13431 hem., cov: 30)
  • Exomes 𝑓: 0.20 (6510 hom. 34328 hem.)
• Consequence: ASMT NM_001171038.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASMT	NM_001171038.2	c.646+44C>T		intron_variant		ENST00000381241.9
ASMT	NM_001171039.1	c.562+2892C>T		intron_variant
ASMT	NM_001416525.1	c.563-319C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASMT	ENST00000381241.9	c.646+44C>T		intron_variant		1	NM_001171038.2
ASMT	ENST00000381229.9	c.563-319C>T		intron_variant		1		P1
ASMT	ENST00000381233.8	c.562+2892C>T		intron_variant		1
ASMT	ENST00000509780.6	n.289-3411C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28189 AN: 150828 Hom.: 2587 Cov.: 30 AF XY: 0.182 AC XY: 13421 AN XY: 73544

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.0570

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.230

GnomAD3 exomes AF: 0.180 AC: 9832 AN: 54638 Hom.: 988 AF XY: 0.183 AC XY: 5049 AN XY: 27608

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.264

Gnomad EAS exome AF: 0.0537

Gnomad SAS exome AF: 0.208

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.198 AC: 65108 AN: 328918 Hom.: 6510 Cov.: 0 AF XY: 0.199 AC XY: 34328 AN XY: 172784

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.0636

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.187 AC: 28191 AN: 150944 Hom.: 2589 Cov.: 30 AF XY: 0.182 AC XY: 13431 AN XY: 73668

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.0569

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.227

Bravo AF: 0.189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7471973; hg19: chrX-1751724;