X-1615250-C-T

Variant names:

• chrX-1615250-C-T
• rs17149149
• NM_001171038.2:c.51C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001171038.2(ASMT):​c.51C>T​(p.Asn17Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000877 in 1,595,808 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 77 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 0.000066 (0 hom., 6 hem., cov: 31)
  • Exomes 𝑓: 0.000090 (0 hom. 71 hem.)
• Consequence: ASMT NM_001171038.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.865 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.51C>T	p.Asn17Asn	synonymous_variant	Exon 1 of 9	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.51C>T	p.Asn17Asn	synonymous_variant	Exon 1 of 8		NP_001403454.1
ASMT	NM_001171039.1	c.51C>T	p.Asn17Asn	synonymous_variant	Exon 1 of 7		NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.51C>T	p.Asn17Asn	synonymous_variant	Exon 1 of 9	1	NM_001171038.2	ENSP00000370639.3
ASMT	ENST00000381229.9	c.51C>T	p.Asn17Asn	synonymous_variant	Exon 1 of 8	1		ENSP00000370627.4
ASMT	ENST00000381233.8	c.51C>T	p.Asn17Asn	synonymous_variant	Exon 1 of 7	1		ENSP00000370631.3

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152070 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000105 AC: 23 AN: 219496 AF XY: 0.000127

Gnomad AFR exome AF: 0.0000734

Gnomad AMR exome AF: 0.0000321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000121

Gnomad FIN exome AF: 0.0000529

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.000180

GnomAD4 exome AF: 0.0000901 AC: 130 AN: 1443620 Hom.: 0 Cov.: 32 AF XY: 0.0000991 AC XY: 71 AN XY: 716128

African (AFR) AF: 0.0000301 AC: 1 AN: 33196

American (AMR) AF: 0.0000239 AC: 1 AN: 41800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25712

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39044

South Asian (SAS) AF: 0.000229 AC: 19 AN: 83020

European-Finnish (FIN) AF: 0.0000767 AC: 4 AN: 52132

Middle Eastern (MID) AF: 0.000523 AC: 3 AN: 5736

European-Non Finnish (NFE) AF: 0.0000825 AC: 91 AN: 1103220

Other (OTH) AF: 0.000117 AC: 7 AN: 59760

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152188 Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6 AN XY: 74394

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Bravo AF: 0.0000642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.023
DANN	Benign	0.88
PhyloP100		-0.86
PromoterAI		-0.0056	Neutral

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

Other links and lift over

dbSNP: rs17149149; hg19: chrX-1734143;