rs117343570

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001171038.2(ASMT):c.241A>G(p.Lys81Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000636 in 1,613,896 control chromosomes in the GnomAD database, including 6 homozygotes. There are 455 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0033 ( 3 hom., 220 hem., cov: 32)

Exomes 𝑓: 0.00036 ( 3 hom. 235 hem. )

Consequence

ASMT
NM_001171038.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.238

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006603956).

BP6

Variant X-1623310-A-G is Benign according to our data. Variant chrX-1623310-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 599440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2 link	c.241A>G	p.Lys81Glu	missense_variant	Exon 2 of 9	ENST00000381241.9	NP_001164509.1	P46597-3A0A024RBT9
ASMT	NM_001416525.1 link	c.241A>G	p.Lys81Glu	missense_variant	Exon 2 of 8		NP_001403454.1
ASMT	NM_001171039.1 link	c.241A>G	p.Lys81Glu	missense_variant	Exon 2 of 7		NP_001164510.1	P46597-2X5D784

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASMT	ENST00000381241.9 link	c.241A>G	p.Lys81Glu	missense_variant	Exon 2 of 9	1	NM_001171038.2	ENSP00000370639.3	P46597-3
ASMT	ENST00000381229.9 link	c.241A>G	p.Lys81Glu	missense_variant	Exon 2 of 8	1		ENSP00000370627.4	P46597-1
ASMT	ENST00000381233.8 link	c.241A>G	p.Lys81Glu	missense_variant	Exon 2 of 7	1		ENSP00000370631.3	P46597-2

Frequencies

GnomAD3 genomes

AF:

0.00333

AC:

506

AN:

152142

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74312

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000877

AC:

220

AN:

250970

Hom.:

AF XY:

0.000708

AC XY:

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.0119

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000355

AC:

519

AN:

1461636

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

235

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.00333

AC:

507

AN:

152260

Hom.:

Cov.:

AF XY:

0.00296

AC XY:

220

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000946

Bravo

AF:

0.00386

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00111

AC:

135

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 05, 2017

Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BS3, BP4; This alteration was found through a well-established in vitro or in vivo functional study to shown no damaging effect on protein function or splicing, and is predicted to be tolerated by multiple functional prediction tools. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0040

DANN

Benign

0.12

DEOGEN2

Benign

0.0029

.;T;.

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.49

T;T;T

MetaRNN

Benign

0.0066

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.52

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.64

T;T;T

Sift4G

Benign

0.69

T;T;T

Polyphen

0.012

B;.;B

Vest4

0.24

MVP

0.52

MPC

0.023

ClinPred

0.00032

GERP RS

-1.0

Varity_R

0.14

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