chrX-1614999-G-C

Variant names:

• chrX-1614999-G-C
• rs5989681
• NM_001171038.2:c.-201G>C

Variant summary

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

The NM_001171038.2(ASMT):​c.-201G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 645,210 control chromosomes in the GnomAD database, including 34,386 homozygotes. There are 101,258 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 (12143 hom., 26832 hem., cov: 31)
  • Exomes 𝑓: 0.29 (22243 hom. 74426 hem.)
• Consequence: ASMT NM_001171038.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.-201G>C		upstream_gene_variant		ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.-201G>C		upstream_gene_variant			NP_001403454.1
ASMT	NM_001171039.1	c.-201G>C		upstream_gene_variant			NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.-201G>C		upstream_gene_variant		1	NM_001171038.2	ENSP00000370639.3
ASMT	ENST00000381229.9	c.-201G>C		upstream_gene_variant		1		ENSP00000370627.4
ASMT	ENST00000381233.8	c.-201G>C		upstream_gene_variant		1		ENSP00000370631.3

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56807 AN: 151556 Hom.: 12124 Cov.: 31 AF XY: 0.362 AC XY: 26767 AN XY: 73956

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.291 AC: 143546 AN: 493536 Hom.: 22243 Cov.: 4 AF XY: 0.285 AC XY: 74426 AN XY: 260906

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.396

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.375 AC: 56874 AN: 151674 Hom.: 12143 Cov.: 31 AF XY: 0.362 AC XY: 26832 AN XY: 74084

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.10
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5989681; hg19: chrX-1733892;