Genetic Variant NM_001171038.2:c.366C>A (chrX-1624390-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001171038.2(ASMT):c.366C>A(p.Asp122Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,070 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D122D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. 5 hem. )

Consequence

ASMT
NM_001171038.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.175

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: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2 link	c.366C>A	p.Asp122Glu	missense_variant	Exon 3 of 9	ENST00000381241.9	NP_001164509.1	P46597-3A0A024RBT9
ASMT	NM_001416525.1 link	c.366C>A	p.Asp122Glu	missense_variant	Exon 3 of 8		NP_001403454.1
ASMT	NM_001171039.1 link	c.366C>A	p.Asp122Glu	missense_variant	Exon 3 of 7		NP_001164510.1	P46597-2X5D784

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASMT	ENST00000381241.9 link	c.366C>A	p.Asp122Glu	missense_variant	Exon 3 of 9	1	NM_001171038.2	ENSP00000370639.3	P46597-3
ASMT	ENST00000381229.9 link	c.366C>A	p.Asp122Glu	missense_variant	Exon 3 of 8	1		ENSP00000370627.4	P46597-1
ASMT	ENST00000381233.8 link	c.366C>A	p.Asp122Glu	missense_variant	Exon 3 of 7	1		ENSP00000370631.3	P46597-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251022

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461070

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726838

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5318

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111800

Other (OTH)

AF:

0.00

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.7

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.0029

.;T;.

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.49

T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;N

PhyloP100

-0.17

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.93

N;N;N

REVEL

Benign

0.043

Sift

Benign

0.84

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.039

B;.;B

Vest4

0.21

MutPred

0.56

Loss of MoRF binding (P = 0.1161);Loss of MoRF binding (P = 0.1161);Loss of MoRF binding (P = 0.1161);

MVP

0.36

MPC

0.022

ClinPred

0.038

GERP RS

-1.5

Varity_R

0.16

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: 3

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

Publications

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NM_001171038.2:c.366C>A

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