Genetic Variant ASMT:c.70-85T>C (chrX-1623054-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001171038.2(ASMT):c.70-85T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,379,922 control chromosomes in the GnomAD database, including 223,102 homozygotes. There are 389,959 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 33246 hom., 47852 hem., cov: 33)

Exomes 𝑓: 0.55 ( 189856 hom. 342107 hem. )

Consequence

ASMT
NM_001171038.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.03

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171038.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ASMT	NM_001171038.2	MANE Select	c.70-85T>C	intron	N/A	NP_001164509.1	P46597-3
ASMT	NM_001416525.1		c.70-85T>C	intron	N/A	NP_001403454.1	X5D2A4
ASMT	NM_001171039.1		c.70-85T>C	intron	N/A	NP_001164510.1	X5D784

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ASMT	ENST00000381241.9	TSL:1 MANE Select	c.70-85T>C	intron	N/A	ENSP00000370639.3	P46597-3
ASMT	ENST00000381229.9	TSL:1	c.70-85T>C	intron	N/A	ENSP00000370627.4	P46597-1
ASMT	ENST00000381233.8	TSL:1	c.70-85T>C	intron	N/A	ENSP00000370631.3	P46597-2

Frequencies

GnomAD3 genomes

AF:

0.643

AC:

97637

AN:

151840

Hom.:

33186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.864

Gnomad AMI

AF:

0.620

Gnomad AMR

AF:

0.692

Gnomad ASJ

AF:

0.602

Gnomad EAS

AF:

0.862

Gnomad SAS

AF:

0.687

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.633

GnomAD4 exome

AF:

0.549

AC:

674746

AN:

1227964

Hom.:

189856

AF XY:

0.553

AC XY:

342107

AN XY:

618590

show subpopulations

African (AFR)

AF:

0.877

AC:

25688

AN:

29276

American (AMR)

AF:

0.743

AC:

31372

AN:

42232

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

15099

AN:

24458

East Asian (EAS)

AF:

0.821

AC:

31428

AN:

38272

South Asian (SAS)

AF:

0.684

AC:

55214

AN:

80726

European-Finnish (FIN)

AF:

0.521

AC:

27438

AN:

52616

Middle Eastern (MID)

AF:

0.649

AC:

2443

AN:

3766

European-Non Finnish (NFE)

AF:

0.504

AC:

455685

AN:

904260

Other (OTH)

AF:

0.580

AC:

30379

AN:

52358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

14197

28394

42592

56789

70986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12476

24952

37428

49904

62380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.643

AC:

97759

AN:

151958

Hom.:

33246

Cov.:

AF XY:

0.645

AC XY:

47852

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.864

AC:

35876

AN:

41530

American (AMR)

AF:

0.692

AC:

10544

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.602

AC:

2088

AN:

3466

East Asian (EAS)

AF:

0.862

AC:

4458

AN:

5172

South Asian (SAS)

AF:

0.687

AC:

3310

AN:

4818

European-Finnish (FIN)

AF:

0.526

AC:

5537

AN:

10530

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.499

AC:

33860

AN:

67892

Other (OTH)

AF:

0.638

AC:

1343

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1578

3156

4733

6311

7889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Bravo

AF:

0.669

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.35

(source)

DANN

Benign

0.20

PhyloP100

-2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over