X-1636511-C-T

Variant names:

• chrX-1636511-C-T
• rs4933063
• NM_001171038.2:c.861C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001171038.2(ASMT):​c.861C>T​(p.Asp287Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 1,613,588 control chromosomes in the GnomAD database, including 8,241 homozygotes. There are 73,489 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.10 (972 hom., 7828 hem., cov: 31)
  • Exomes 𝑓: 0.092 (7269 hom. 65661 hem.)
• Consequence: ASMT NM_001171038.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0960
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant X-1636511-C-T is Benign according to our data. Variant chrX-1636511-C-T is described in ClinVar as [Benign]. Clinvar id is 3036285.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.096 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.861C>T	p.Asp287Asp	synonymous_variant	Exon 8 of 9	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.777C>T	p.Asp259Asp	synonymous_variant	Exon 7 of 8		NP_001403454.1
ASMT	NM_001171039.1	c.636C>T	p.Asp212Asp	synonymous_variant	Exon 6 of 7		NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.861C>T	p.Asp287Asp	synonymous_variant	Exon 8 of 9	1	NM_001171038.2	ENSP00000370639.3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15870 AN: 151944 Hom.: 974 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0792

Gnomad OTH AF: 0.0869

GnomAD2 exomes AF: 0.106 AC: 26690 AN: 251166 AF XY: 0.0999

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.0653

Gnomad EAS exome AF: 0.287

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.0765

Gnomad OTH exome AF: 0.0928

GnomAD4 exome AF: 0.0916 AC: 133892 AN: 1461526 Hom.: 7269 Cov.: 32 AF XY: 0.0903 AC XY: 65661 AN XY: 727040

African (AFR) AF: 0.125 AC: 4192 AN: 33470

American (AMR) AF: 0.145 AC: 6475 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 1800 AN: 26132

East Asian (EAS) AF: 0.284 AC: 11265 AN: 39692

South Asian (SAS) AF: 0.0667 AC: 5754 AN: 86240

European-Finnish (FIN) AF: 0.102 AC: 5467 AN: 53420

Middle Eastern (MID) AF: 0.0684 AC: 394 AN: 5762

European-Non Finnish (NFE) AF: 0.0830 AC: 92295 AN: 1111722

Other (OTH) AF: 0.104 AC: 6250 AN: 60376

GnomAD4 genome AF: 0.104 AC: 15880 AN: 152062 Hom.: 972 Cov.: 31 AF XY: 0.105 AC XY: 7828 AN XY: 74338

African (AFR) AF: 0.129 AC: 5351 AN: 41476

American (AMR) AF: 0.111 AC: 1699 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 248 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1440 AN: 5164

South Asian (SAS) AF: 0.0706 AC: 340 AN: 4816

European-Finnish (FIN) AF: 0.111 AC: 1173 AN: 10580

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0792 AC: 5384 AN: 67982

Other (OTH) AF: 0.0859 AC: 181 AN: 2106

Bravo AF: 0.108

EpiCase AF: 0.0786

EpiControl AF: 0.0736

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ASMT-related disorder Benign:1

Feb 16, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.0060
DANN	Benign	0.58
PhyloP100		0.096
PromoterAI		-0.048	Neutral

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: rs4933063; hg19: chrX-1755404; COSMIC: COSV67110370; COSMIC: COSV67110370;