Genetic Variant ASMT:c.-201G>C (chrX-1614999-G-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.-201G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 645,210 control chromosomes in the GnomAD database, including 34,386 homozygotes. There are 101,258 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 0.37 ( 12143 hom., 26832 hem., cov: 31)

Exomes 𝑓: 0.29 ( 22243 hom. 74426 hem. )

Consequence

ASMT
NM_001171038.2 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.61

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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ASMT	NM_001171038.2 link	c.-201G>C	upstream_gene_variant	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1 link	c.-201G>C	upstream_gene_variant		NP_001403454.1
ASMT	NM_001171039.1 link	c.-201G>C	upstream_gene_variant		NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein
ASMT	ENST00000381241.9 link	c.-201G>C	upstream_gene_variant	1	NM_001171038.2	ENSP00000370639.3
ASMT	ENST00000381229.9 link	c.-201G>C	upstream_gene_variant	1		ENSP00000370627.4
ASMT	ENST00000381233.8 link	c.-201G>C	upstream_gene_variant	1		ENSP00000370631.3

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

56807

AN:

151556

Hom.:

12124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.613

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.352

GnomAD4 exome

AF:

0.291

AC:

143546

AN:

493536

Hom.:

22243

Cov.:

AF XY:

0.285

AC XY:

74426

AN XY:

260906

show subpopulations

African (AFR)

AF:

0.607

AC:

8424

AN:

13880

American (AMR)

AF:

0.393

AC:

10180

AN:

25924

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

3740

AN:

15374

East Asian (EAS)

AF:

0.396

AC:

12434

AN:

31410

South Asian (SAS)

AF:

0.222

AC:

11028

AN:

49574

European-Finnish (FIN)

AF:

0.144

AC:

6249

AN:

43502

Middle Eastern (MID)

AF:

0.252

AC:

531

AN:

2108

European-Non Finnish (NFE)

AF:

0.291

AC:

82670

AN:

284230

Other (OTH)

AF:

0.301

AC:

8290

AN:

27534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

5132

10264

15397

20529

25661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.375

AC:

56874

AN:

151674

Hom.:

12143

Cov.:

AF XY:

0.362

AC XY:

26832

AN XY:

74084

show subpopulations

African (AFR)

AF:

0.613

AC:

25297

AN:

41278

American (AMR)

AF:

0.356

AC:

5398

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

838

AN:

3462

East Asian (EAS)

AF:

0.414

AC:

2133

AN:

5148

South Asian (SAS)

AF:

0.213

AC:

1028

AN:

4818

European-Finnish (FIN)

AF:

0.137

AC:

1445

AN:

10560

Middle Eastern (MID)

AF:

0.257

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.290

AC:

19677

AN:

67914

Other (OTH)

AF:

0.350

AC:

738

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1597

3194

4790

6387

7984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.10

(source)

DANN

Benign

0.28

PhyloP100

-1.6

PromoterAI

0.010

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over