Variant X-1636567-TG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001171038.2(ASMT):c.910+8del 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 (★).

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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.602

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 -10 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 id is 3036440.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ASMT	NM_001171038.2 linkuse as main transcript	c.910+8del	splice_region_variant, intron_variant	ENST00000381241.9
ASMT	NM_001171039.1 linkuse as main transcript	c.685+8del	splice_region_variant, intron_variant
ASMT	NM_001416525.1 linkuse as main transcript	c.826+8del	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ASMT	ENST00000381241.9 linkuse as main transcript	c.910+8del	splice_region_variant, intron_variant	1	NM_001171038.2		P46597-3
ASMT	ENST00000381229.9 linkuse as main transcript	c.826+8del	splice_region_variant, intron_variant	1		P1	P46597-1
ASMT	ENST00000381233.8 linkuse as main transcript	c.685+8del	splice_region_variant, intron_variant	1			P46597-2
ASMT	ENST00000432523.6 linkuse as main transcript	c.163+8del	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22812

AN:

152054

Hom.:

1825

Cov.:

AF XY:

0.150

AC XY:

11144

AN XY:

74256

show subpopulations

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

GnomAD3 exomes

AF:

0.137

AC:

34409

AN:

251148

Hom.:

2618

AF XY:

0.139

AC XY:

18803

AN XY:

135718

show subpopulations

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 SAS exome

AF:

0.206

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.:

AF XY:

0.131

AC XY:

95000

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.0795

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.150

AC:

22821

AN:

152172

Hom.:

1827

Cov.:

AF XY:

0.150

AC XY:

11156

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.0758

Gnomad4 SAS

AF:

0.198

Gnomad4 FIN

AF:

0.128

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.148

Bravo

AF:

0.150

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ASMT-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2021

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

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