rs11346829

Variant names:

• chrX-1636567-TG-T
• rs11346829
• NM_001171038.2:c.910+8delG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001171038.2(ASMT):​c.910+8delG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,694 control chromosomes in the GnomAD database, including 14,561 homozygotes. There are 106,156 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (1827 hom., 11156 hem., cov: 29)
  • Exomes 𝑓: 0.13 (12734 hom. 95000 hem.)
• Consequence: ASMT NM_001171038.2 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.602
• 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 -9 ACMG points.

• BP6: Variant X-1636567-TG-T is Benign according to our data. Variant chrX-1636567-TG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3036440.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.910+8delG		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.826+8delG		splice_region_variant, intron_variant	Intron 7 of 7		NP_001403454.1
ASMT	NM_001171039.1	c.685+8delG		splice_region_variant, intron_variant	Intron 6 of 6		NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.910+8delG		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_001171038.2	ENSP00000370639.3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22812 AN: 152054 Hom.: 1825 Cov.: 29

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0756

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.151

GnomAD2 exomes AF: 0.137 AC: 34409 AN: 251148 AF XY: 0.139

Gnomad AFR exome AF: 0.221

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.0757

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.129 AC: 187905 AN: 1461522 Hom.: 12734 Cov.: 31 AF XY: 0.131 AC XY: 95000 AN XY: 727036

African (AFR) AF: 0.212 AC: 7106 AN: 33466

American (AMR) AF: 0.136 AC: 6101 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 4105 AN: 26124

East Asian (EAS) AF: 0.0795 AC: 3155 AN: 39698

South Asian (SAS) AF: 0.199 AC: 17122 AN: 86246

European-Finnish (FIN) AF: 0.110 AC: 5883 AN: 53416

Middle Eastern (MID) AF: 0.153 AC: 878 AN: 5750

European-Non Finnish (NFE) AF: 0.122 AC: 135435 AN: 1111740

Other (OTH) AF: 0.135 AC: 8120 AN: 60368

GnomAD4 genome AF: 0.150 AC: 22821 AN: 152172 Hom.: 1827 Cov.: 29 AF XY: 0.150 AC XY: 11156 AN XY: 74384

African (AFR) AF: 0.216 AC: 8950 AN: 41502

American (AMR) AF: 0.119 AC: 1823 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3472

East Asian (EAS) AF: 0.0758 AC: 393 AN: 5184

South Asian (SAS) AF: 0.198 AC: 957 AN: 4828

European-Finnish (FIN) AF: 0.128 AC: 1352 AN: 10592

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8353 AN: 68002

Other (OTH) AF: 0.148 AC: 313 AN: 2114

Bravo AF: 0.150

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ASMT-related disorder Benign:1

Feb 22, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.60
Mutation Taster		=95/5	polymorphism

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: rs11346829; hg19: chrX-1755460; COSMIC: COSV107494728; COSMIC: COSV107494728;