X-1629688-A-G

Variant names:

• chrX-1629688-A-G
• rs6588807
• NM_001171038.2:c.444-133A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001171038.2(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 NM_001171038.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 rank	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.444-133A>G		intron_variant	Intron 4 of 8	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.444-133A>G		intron_variant	Intron 4 of 7		NP_001403454.1
ASMT	NM_001171039.1	c.444-133A>G		intron_variant	Intron 4 of 6		NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.444-133A>G		intron_variant	Intron 4 of 8	1	NM_001171038.2	ENSP00000370639.3
ASMT	ENST00000381229.9	c.444-133A>G		intron_variant	Intron 4 of 7	1		ENSP00000370627.4
ASMT	ENST00000381233.8	c.444-133A>G		intron_variant	Intron 4 of 6	1		ENSP00000370631.3
ASMT	ENST00000509780.6	n.288+1655A>G		intron_variant	Intron 1 of 1	1

Frequencies

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

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

African (AFR) AF: 0.000152 AC: 3 AN: 19740

American (AMR) AF: 0.0000230 AC: 1 AN: 43468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21428

East Asian (EAS) AF: 0.0000276 AC: 1 AN: 36190

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 71158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3104

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 430048

Other (OTH) AF: 0.0000280 AC: 1 AN: 35722

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

African (AFR) AF: 0.00 AC: 0 AN: 41342

American (AMR) AF: 0.0000657 AC: 1 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2090

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
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs6588807; hg19: chrX-1748581;