Variant X-1636511-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The ENST00000381241.9(ASMT):c.861C>T(p.Asp287=) 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
ENST00000381241.9 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0960

Variant links:

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]

ASMT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein
ASMT	NM_001171038.2 linkuse as main transcript	c.861C>T	p.Asp287=	synonymous_variant	8/9	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1 linkuse as main transcript	c.777C>T	p.Asp259=	synonymous_variant	7/8		NP_001403454.1
ASMT	NM_001171039.1 linkuse as main transcript	c.636C>T	p.Asp212=	synonymous_variant	6/7		NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9 linkuse as main transcript	c.861C>T	p.Asp287=	synonymous_variant	8/9	1	NM_001171038.2	ENSP00000370639		P46597-3

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15870

AN:

151944

Hom.:

974

Cov.:

AF XY:

0.105

AC XY:

7810

AN XY:

74210

show subpopulations

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

GnomAD3 exomes

AF:

0.106

AC:

26690

AN:

251166

Hom.:

1928

AF XY:

0.0999

AC XY:

13556

AN XY:

135728

show subpopulations

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 SAS exome

AF:

0.0652

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.:

AF XY:

0.0903

AC XY:

65661

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.0689

Gnomad4 EAS exome

AF:

0.284

Gnomad4 SAS exome

AF:

0.0667

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.0830

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.104

AC:

15880

AN:

152062

Hom.:

972

Cov.:

AF XY:

0.105

AC XY:

7828

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.0715

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.0706

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.0792

Gnomad4 OTH

AF:

0.0859

Bravo

AF:

0.108

EpiCase

AF:

0.0786

EpiControl

AF:

0.0736

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ASMT-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 16, 2021

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over