Genetic Variant NM_001171038.2:c.630C>T (chrX-1632771-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001171038.2(ASMT):c.630C>T(p.Arg210Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000834 in 359,852 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. Synonymous variant affecting the same amino acid position (i.e. R210R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., 0 hem., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. 1 hem. )

Consequence

ASMT
NM_001171038.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.108

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 -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP7

Synonymous conserved (PhyloP=0.108 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2 link	c.630C>T	p.Arg210Arg	synonymous_variant	Exon 6 of 9	ENST00000381241.9	NP_001164509.1	P46597-3A0A024RBT9
ASMT	NM_001416525.1 link	c.563-379C>T		intron_variant	Intron 5 of 7		NP_001403454.1
ASMT	NM_001171039.1 link	c.562+2832C>T		intron_variant	Intron 5 of 6		NP_001164510.1	P46597-2X5D784

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASMT	ENST00000381241.9 link	c.630C>T	p.Arg210Arg	synonymous_variant	Exon 6 of 9	1	NM_001171038.2	ENSP00000370639.3	P46597-3
ASMT	ENST00000381229.9 link	c.563-379C>T		intron_variant	Intron 5 of 7	1		ENSP00000370627.4	P46597-1
ASMT	ENST00000381233.8 link	c.562+2832C>T		intron_variant	Intron 5 of 6	1		ENSP00000370631.3	P46597-2
ASMT	ENST00000509780.6 link	n.289-3471C>T		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000962

AC:

AN:

207874

Hom.:

Cov.:

AF XY:

0.00000914

AC XY:

AN XY:

109394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7108

American (AMR)

AF:

0.00

AC:

AN:

10250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5778

East Asian (EAS)

AF:

0.00

AC:

AN:

10914

South Asian (SAS)

AF:

0.0000332

AC:

AN:

30146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

882

European-Non Finnish (NFE)

AF:

0.00000821

AC:

AN:

121828

Other (OTH)

AF:

0.00

AC:

AN:

11424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151978

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Bravo

AF:

0.0000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.99

(source)

DANN

Benign

0.53

PhyloP100

0.11

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

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NM_001171038.2:c.630C>T

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