dbSNP rs6644635: ASMT:c.-99T>A (chrX-1615101-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001171038.2(ASMT):c.-99T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 998,184 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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 0.000013 ( 0 hom., 1 hem., cov: 31)

Exomes 𝑓: 0.0000095 ( 0 hom. 5 hem. )

Consequence

ASMT
NM_001171038.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.83

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2 link	c.-99T>A	5_prime_UTR_variant	Exon 1 of 9	ENST00000381241.9	NP_001164509.1	P46597-3A0A024RBT9
ASMT	NM_001416525.1 link	c.-99T>A	5_prime_UTR_variant	Exon 1 of 8		NP_001403454.1
ASMT	NM_001171039.1 link	c.-99T>A	upstream_gene_variant			NP_001164510.1	P46597-2X5D784

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASMT	ENST00000381241.9 link	c.-99T>A	5_prime_UTR_variant	Exon 1 of 9	1	NM_001171038.2	ENSP00000370639.3	P46597-3
ASMT	ENST00000381229.9 link	c.-99T>A	upstream_gene_variant		1		ENSP00000370627.4	P46597-1
ASMT	ENST00000381233.8 link	c.-99T>A	upstream_gene_variant		1		ENSP00000370631.3	P46597-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000945

AC:

AN:

846330

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

436534

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21678

American (AMR)

AF:

0.0000285

AC:

AN:

35046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21758

East Asian (EAS)

AF:

0.00

AC:

AN:

33246

South Asian (SAS)

AF:

0.0000146

AC:

AN:

68440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3826

European-Non Finnish (NFE)

AF:

0.0000105

AC:

AN:

573520

Other (OTH)

AF:

0.00

AC:

AN:

39756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151854

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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

-0.89

CADD

Benign

0.011

(source)

DANN

Benign

0.38

PhyloP100

-4.8

PromoterAI

0.034

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over