rs6644635

Positions:

• chrX-1615101-T-A
• chrX-1615101-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001171038.2(ASMT):​c.-99T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 998,184 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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 0.000013 (0 hom., 1 hem., cov: 31)
  • Exomes 𝑓: 0.0000095 (0 hom. 5 hem.)
• Consequence: ASMT NM_001171038.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASMT	NM_001171038.2	c.-99T>A		5_prime_UTR_variant	1/9	ENST00000381241.9
ASMT	NM_001416525.1	c.-99T>A		5_prime_UTR_variant	1/8
ASMT	NM_001171039.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASMT	ENST00000381241.9	c.-99T>A		5_prime_UTR_variant	1/9	1	NM_001171038.2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151854 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74148

Gnomad AFR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000945 AC: 8 AN: 846330 Hom.: 0 Cov.: 11 AF XY: 0.0000115 AC XY: 5 AN XY: 436534

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000285

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000146

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000105

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151854 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74148

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.011
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6644635; hg19: chrX-1733994;