rs17149149

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001171038.2(ASMT):c.51C>A(p.Asn17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,595,758 control chromosomes in the GnomAD database, including 126 homozygotes. There are 3,268 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0030 ( 8 hom., 273 hem., cov: 31)

Exomes 𝑓: 0.0031 ( 118 hom. 2995 hem. )

Consequence

ASMT
NM_001171038.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -0.865

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063019395).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00298 (453/152184) while in subpopulation SAS AF = 0.0386 (186/4824). AF 95% confidence interval is 0.034. There are 8 homozygotes in GnomAd4. There are 273 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2 link	c.51C>A	p.Asn17Lys	missense_variant	Exon 1 of 9	ENST00000381241.9	NP_001164509.1	P46597-3A0A024RBT9
ASMT	NM_001416525.1 link	c.51C>A	p.Asn17Lys	missense_variant	Exon 1 of 8		NP_001403454.1
ASMT	NM_001171039.1 link	c.51C>A	p.Asn17Lys	missense_variant	Exon 1 of 7		NP_001164510.1	P46597-2X5D784

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASMT	ENST00000381241.9 link	c.51C>A	p.Asn17Lys	missense_variant	Exon 1 of 9	1	NM_001171038.2	ENSP00000370639.3	P46597-3
ASMT	ENST00000381229.9 link	c.51C>A	p.Asn17Lys	missense_variant	Exon 1 of 8	1		ENSP00000370627.4	P46597-1
ASMT	ENST00000381233.8 link	c.51C>A	p.Asn17Lys	missense_variant	Exon 1 of 7	1		ENSP00000370631.3	P46597-2

Frequencies

GnomAD3 genomes

AF:

0.00295

AC:

449

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000788

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0278

Gnomad SAS

AF:

0.0383

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00680

AC:

1492

AN:

219496

AF XY:

0.00843

show subpopulations

Gnomad AFR exome

AF:

0.00279

Gnomad AMR exome

AF:

0.000739

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0279

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.00216

GnomAD4 exome

AF:

0.00312

AC:

4501

AN:

1443574

Hom.:

118

Cov.:

AF XY:

0.00418

AC XY:

2995

AN XY:

716094

show subpopulations

African (AFR)

AF:

0.00232

AC:

AN:

33192

American (AMR)

AF:

0.000670

AC:

AN:

41800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25712

East Asian (EAS)

AF:

0.0225

AC:

879

AN:

39034

South Asian (SAS)

AF:

0.0382

AC:

3168

AN:

82990

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52132

Middle Eastern (MID)

AF:

0.00314

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.0000625

AC:

AN:

1103218

Other (OTH)

AF:

0.00438

AC:

262

AN:

59760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

251

501

752

1002

1253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00298

AC:

453

AN:

152184

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

273

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41556

American (AMR)

AF:

0.000787

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0279

AC:

144

AN:

5166

South Asian (SAS)

AF:

0.0386

AC:

186

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68000

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Bravo

AF:

0.00242

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00652

AC:

789

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Nov 13, 2023

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ASMT-related disorder

Benign:1

Sep 20, 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

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.8

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.014

.;T;.

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.0063

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.8

M;M;M

PhyloP100

-0.86

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.14

Sift

Benign

0.044

D;T;T

Sift4G

Uncertain

0.057

T;T;T

Polyphen

0.99

D;.;D

Vest4

0.23

MutPred

0.86

Gain of ubiquitination at N17 (P = 0.0388);Gain of ubiquitination at N17 (P = 0.0388);Gain of ubiquitination at N17 (P = 0.0388);

MVP

0.43

MPC

0.10

ClinPred

0.048

GERP RS

-2.3

PromoterAI

-0.036

Neutral

(source)

Varity_R

0.32

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs17149149

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over