NM_001171038.2:c.647-26G>T

Variant names:

• chrX-1633124-G-T
• rs4521942
• NM_001171038.2:c.647-26G>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.647-26G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 1,612,248 control chromosomes in the GnomAD database, including 6,866 homozygotes. There are 74,863 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 0.10 (798 hom., 7585 hem., cov: 32)
  • Exomes 𝑓: 0.089 (6068 hom. 67278 hem.)
• Consequence: ASMT NM_001171038.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.647-26G>T		intron_variant	Intron 6 of 8	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.563-26G>T		intron_variant	Intron 5 of 7		NP_001403454.1
ASMT	NM_001171039.1	c.562+3185G>T		intron_variant	Intron 5 of 6		NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.647-26G>T		intron_variant	Intron 6 of 8	1	NM_001171038.2	ENSP00000370639.3
ASMT	ENST00000381229.9	c.563-26G>T		intron_variant	Intron 5 of 7	1		ENSP00000370627.4
ASMT	ENST00000381233.8	c.562+3185G>T		intron_variant	Intron 5 of 6	1		ENSP00000370631.3
ASMT	ENST00000509780.6	n.289-3118G>T		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15612 AN: 151794 Hom.: 796 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0947

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0433

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0615

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.100 AC: 25146 AN: 250994 AF XY: 0.104

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.0989

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.0518

Gnomad FIN exome AF: 0.0617

Gnomad NFE exome AF: 0.0836

Gnomad OTH exome AF: 0.0974

GnomAD4 exome AF: 0.0895 AC: 130696 AN: 1460336 Hom.: 6068 Cov.: 34 AF XY: 0.0926 AC XY: 67278 AN XY: 726402

African (AFR) AF: 0.136 AC: 4554 AN: 33374

American (AMR) AF: 0.100 AC: 4467 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3588 AN: 26116

East Asian (EAS) AF: 0.0469 AC: 1862 AN: 39698

South Asian (SAS) AF: 0.180 AC: 15516 AN: 86002

European-Finnish (FIN) AF: 0.0644 AC: 3440 AN: 53414

Middle Eastern (MID) AF: 0.138 AC: 793 AN: 5742

European-Non Finnish (NFE) AF: 0.0816 AC: 90676 AN: 1110972

Other (OTH) AF: 0.0961 AC: 5800 AN: 60330

GnomAD4 genome AF: 0.103 AC: 15621 AN: 151912 Hom.: 798 Cov.: 32 AF XY: 0.102 AC XY: 7585 AN XY: 74258

African (AFR) AF: 0.142 AC: 5887 AN: 41326

American (AMR) AF: 0.0945 AC: 1439 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3470

East Asian (EAS) AF: 0.0432 AC: 224 AN: 5182

South Asian (SAS) AF: 0.188 AC: 904 AN: 4810

European-Finnish (FIN) AF: 0.0615 AC: 652 AN: 10598

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0836 AC: 5683 AN: 67982

Other (OTH) AF: 0.112 AC: 237 AN: 2110

Bravo AF: 0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.019
DANN	Benign	0.42
PhyloP100		-0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4521942; hg19: chrX-1752017; COSMIC: COSV67109922; COSMIC: COSV67109922;