rs6588807

Positions:

• chrX-1629688-A-C
• chrX-1629688-A-G

Variant summary

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

The ENST00000381241.9(ASMT):​c.444-133A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 863,660 control chromosomes in the GnomAD database, including 51,610 homozygotes. There are 159,183 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 0.37 (9712 hom., 27031 hem., cov: 32)
  • Exomes 𝑓: 0.35 (41898 hom. 132152 hem.)
• Consequence: ASMT ENST00000381241.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.444-133A>C		intron_variant		ENST00000381241.9	NP_001164509.1
ASMT	NM_001171039.1	c.444-133A>C		intron_variant			NP_001164510.1
ASMT	NM_001416525.1	c.444-133A>C		intron_variant			NP_001403454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.444-133A>C		intron_variant		1	NM_001171038.2	ENSP00000370639
ASMT	ENST00000381229.9	c.444-133A>C		intron_variant		1		ENSP00000370627	P1
ASMT	ENST00000381233.8	c.444-133A>C		intron_variant		1		ENSP00000370631
ASMT	ENST00000509780.6	n.288+1655A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55384 AN: 151488 Hom.: 9706 Cov.: 32 AF XY: 0.365 AC XY: 26985 AN XY: 73956

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.348 AC: 247610 AN: 712054 Hom.: 41898 AF XY: 0.348 AC XY: 132152 AN XY: 379782

Gnomad4 AFR exome AF: 0.430

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.368

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.366 AC: 55427 AN: 151606 Hom.: 9712 Cov.: 32 AF XY: 0.365 AC XY: 27031 AN XY: 74084

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.369

Bravo AF: 0.366

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
DANN	Benign	0.14

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: rs6588807; hg19: chrX-1748581; COSMIC: COSV67109620;