Genetic Variant ASMT:c.646+44C>T (chrX-1632831-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001171038.2(ASMT):c.646+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 479,862 control chromosomes in the GnomAD database, including 9,099 homozygotes. There are 47,759 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 0.19 ( 2589 hom., 13431 hem., cov: 30)

Exomes 𝑓: 0.20 ( 6510 hom. 34328 hem. )

Consequence

ASMT
NM_001171038.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.108

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2 link	c.646+44C>T	intron_variant	Intron 6 of 8	ENST00000381241.9	NP_001164509.1	P46597-3A0A024RBT9
ASMT	NM_001416525.1 link	c.563-319C>T	intron_variant	Intron 5 of 7		NP_001403454.1
ASMT	NM_001171039.1 link	c.562+2892C>T	intron_variant	Intron 5 of 6		NP_001164510.1	P46597-2X5D784

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASMT	ENST00000381241.9 link	c.646+44C>T	intron_variant	Intron 6 of 8	1	NM_001171038.2	ENSP00000370639.3	P46597-3
ASMT	ENST00000381229.9 link	c.563-319C>T	intron_variant	Intron 5 of 7	1		ENSP00000370627.4	P46597-1
ASMT	ENST00000381233.8 link	c.562+2892C>T	intron_variant	Intron 5 of 6	1		ENSP00000370631.3	P46597-2
ASMT	ENST00000509780.6 link	n.289-3411C>T	intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28189

AN:

150828

Hom.:

2587

Cov.:

AF XY:

0.182

AC XY:

13421

AN XY:

73544

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.0570

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.230

GnomAD3 exomes

AF:

0.180

AC:

9832

AN:

54638

Hom.:

988

AF XY:

0.183

AC XY:

5049

AN XY:

27608

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.0537

Gnomad SAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.198

AC:

65108

AN:

328918

Hom.:

6510

Cov.:

AF XY:

0.199

AC XY:

34328

AN XY:

172784

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.260

Gnomad4 EAS exome

AF:

0.0636

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.187

AC:

28191

AN:

150944

Hom.:

2589

Cov.:

AF XY:

0.182

AC XY:

13431

AN XY:

73668

show subpopulations

Gnomad4 AFR

AF:

0.167

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.253

Gnomad4 EAS

AF:

0.0569

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.113

Gnomad4 NFE

AF:

0.216

Gnomad4 OTH

AF:

0.227

Bravo

AF:

0.189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.4

DANN

Benign

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over