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. The variant received -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
• 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: Benign. The variant received -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

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

African (AFR) AF: 0.0457 AC: 529 AN: 11576

American (AMR) AF: 0.199 AC: 3371 AN: 16946

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 2832 AN: 12326

East Asian (EAS) AF: 0.282 AC: 7762 AN: 27572

South Asian (SAS) AF: 0.167 AC: 6749 AN: 40502

European-Finnish (FIN) AF: 0.130 AC: 3374 AN: 25984

Middle Eastern (MID) AF: 0.213 AC: 373 AN: 1750

European-Non Finnish (NFE) AF: 0.252 AC: 59414 AN: 235880

Other (OTH) AF: 0.213 AC: 4916 AN: 23118

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

African (AFR) AF: 0.0445 AC: 1846 AN: 41514

American (AMR) AF: 0.207 AC: 3141 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3466

East Asian (EAS) AF: 0.282 AC: 1450 AN: 5150

South Asian (SAS) AF: 0.164 AC: 784 AN: 4790

European-Finnish (FIN) AF: 0.126 AC: 1334 AN: 10566

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17059 AN: 67882

Other (OTH) AF: 0.202 AC: 426 AN: 2104

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
PhyloP100		0.11
PromoterAI		0.040	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4446909; hg19: chrX-1733783;