X-1636773-C-T

Variant names:

• chrX-1636773-C-T
• rs5949028
• NM_001171038.2:c.910+213C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001171038.2(ASMT):​c.910+213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,066 control chromosomes in the GnomAD database, including 13,317 homozygotes. There are 31,328 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 0.41 (13317 hom., 31328 hem., cov: 33)
• Consequence: ASMT NM_001171038.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171038.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASMT	NM_001171038.2	MANE Select	c.910+213C>T		intron	N/A	NP_001164509.1	P46597-3
	ASMT	NM_001416525.1		c.826+213C>T		intron	N/A	NP_001403454.1	X5D2A4
	ASMT	NM_001171039.1		c.685+213C>T		intron	N/A	NP_001164510.1	X5D784

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASMT	ENST00000381241.9	TSL:1 MANE Select	c.910+213C>T		intron	N/A	ENSP00000370639.3	P46597-3
	ASMT	ENST00000381229.9	TSL:1	c.826+213C>T		intron	N/A	ENSP00000370627.4	P46597-1
	ASMT	ENST00000381233.8	TSL:1	c.685+213C>T		intron	N/A	ENSP00000370631.3	P46597-2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62965 AN: 151948 Hom.: 13295 Cov.: 33

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.414

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.415 AC: 63036 AN: 152066 Hom.: 13317 Cov.: 33 AF XY: 0.422 AC XY: 31328 AN XY: 74306

African (AFR) AF: 0.411 AC: 17049 AN: 41520

American (AMR) AF: 0.419 AC: 6399 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1565 AN: 3468

East Asian (EAS) AF: 0.689 AC: 3567 AN: 5176

South Asian (SAS) AF: 0.399 AC: 1920 AN: 4818

European-Finnish (FIN) AF: 0.516 AC: 5449 AN: 10558

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25744 AN: 67940

Other (OTH) AF: 0.418 AC: 882 AN: 2110

Bravo AF: 0.408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.33
DANN	Benign	0.29
PhyloP100		-1.8
PromoterAI		-0.028	Neutral
Mutation Taster		=9/91	disease causing

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: rs5949028; hg19: chrX-1755666;