X-1623054-T-C

Variant names:

• chrX-1623054-T-C
• rs6588802
• NM_001171038.2:c.70-85T>C

Variant summary

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

The NM_001171038.2(ASMT):​c.70-85T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,379,922 control chromosomes in the GnomAD database, including 223,102 homozygotes. There are 389,959 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 0.64 (33246 hom., 47852 hem., cov: 33)
  • Exomes 𝑓: 0.55 (189856 hom. 342107 hem.)
• Consequence: ASMT NM_001171038.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.70-85T>C		intron_variant	Intron 1 of 8	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.70-85T>C		intron_variant	Intron 1 of 7		NP_001403454.1
ASMT	NM_001171039.1	c.70-85T>C		intron_variant	Intron 1 of 6		NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.70-85T>C		intron_variant	Intron 1 of 8	1	NM_001171038.2	ENSP00000370639.3
ASMT	ENST00000381229.9	c.70-85T>C		intron_variant	Intron 1 of 7	1		ENSP00000370627.4
ASMT	ENST00000381233.8	c.70-85T>C		intron_variant	Intron 1 of 6	1		ENSP00000370631.3

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97637 AN: 151840 Hom.: 33186 Cov.: 33 AF XY: 0.644 AC XY: 47736 AN XY: 74102

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.633

GnomAD4 exome AF: 0.549 AC: 674746 AN: 1227964 Hom.: 189856 AF XY: 0.553 AC XY: 342107 AN XY: 618590

Gnomad4 AFR exome AF: 0.877

Gnomad4 AMR exome AF: 0.743

Gnomad4 ASJ exome AF: 0.617

Gnomad4 EAS exome AF: 0.821

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.580

GnomAD4 genome AF: 0.643 AC: 97759 AN: 151958 Hom.: 33246 Cov.: 33 AF XY: 0.645 AC XY: 47852 AN XY: 74230

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.862

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.638

Bravo AF: 0.669

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6588802; hg19: chrX-1741947;