rs4446909

Variant names:

• chrX-1614890-G-A
• rs4446909
• NM_001171038.2:c.-310G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-1614890-G-A
• chrX-1614890-G-T

Variant summary

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

The NM_001171038.2(ASMT):​c.-310G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 547,538 control chromosomes in the GnomAD database, including 13,448 homozygotes. There are 59,167 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 0.18 (2901 hom., 12929 hem., cov: 31)
  • Exomes 𝑓: 0.23 (10547 hom. 46238 hem.)
• Consequence: ASMT NM_001171038.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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 (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.-310G>A		upstream_gene_variant		ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.-310G>A		upstream_gene_variant			NP_001403454.1
ASMT	NM_001171039.1	c.-310G>A		upstream_gene_variant			NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.-310G>A		upstream_gene_variant		1	NM_001171038.2	ENSP00000370639.3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27110 AN: 151766 Hom.: 2906 Cov.: 31 AF XY: 0.175 AC XY: 12930 AN XY: 74080

Gnomad AFR AF: 0.0446

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.226 AC: 89320 AN: 395654 Hom.: 10547 AF XY: 0.224 AC XY: 46238 AN XY: 206338

Gnomad4 AFR exome AF: 0.0457

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.178 AC: 27095 AN: 151884 Hom.: 2901 Cov.: 31 AF XY: 0.174 AC XY: 12929 AN XY: 74208

Gnomad4 AFR AF: 0.0445

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.202

Bravo AF: 0.181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4446909; hg19: chrX-1733783;