X-1629688-A-G

Position:

• chrX-1629688-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000381241.9(ASMT):​c.444-133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,856 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.000013 (0 hom., 0 hem., cov: 32)
  • Exomes 𝑓: 0.0000098 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151856 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74140

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000981 AC: 7 AN: 713852 Hom.: 0 AF XY: 0.00000788 AC XY: 3 AN XY: 380766

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.0000230

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000276

Gnomad4 SAS exome AF: 0.0000141

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000280

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151856 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74140

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.14

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: rs6588807; hg19: chrX-1748581;