X-1615101-T-C

Variant names:

• chrX-1615101-T-C
• rs6644635
• NM_001171038.2:c.-99T>C

Variant summary

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

The NM_001171038.2(ASMT):​c.-99T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 996,040 control chromosomes in the GnomAD database, including 206,718 homozygotes. There are 327,764 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 0.68 (34930 hom., 50123 hem., cov: 31)
  • Exomes 𝑓: 0.64 (171788 hom. 277641 hem.)
• Consequence: ASMT NM_001171038.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83
• 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 (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.-99T>C		5_prime_UTR_variant	Exon 1 of 9	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.-99T>C		5_prime_UTR_variant	Exon 1 of 8		NP_001403454.1
ASMT	NM_001171039.1	c.-99T>C		upstream_gene_variant			NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.-99T>C		5_prime_UTR_variant	Exon 1 of 9	1	NM_001171038.2	ENSP00000370639.3
ASMT	ENST00000381229.9	c.-99T>C		upstream_gene_variant		1		ENSP00000370627.4
ASMT	ENST00000381233.8	c.-99T>C		upstream_gene_variant		1		ENSP00000370631.3

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102818 AN: 151632 Hom.: 34886 Cov.: 31

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.640 AC: 540107 AN: 844290 Hom.: 171788 Cov.: 11 AF XY: 0.638 AC XY: 277641 AN XY: 435500

African (AFR) AF: 0.786 AC: 16989 AN: 21620

American (AMR) AF: 0.686 AC: 23990 AN: 34988

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 13125 AN: 21738

East Asian (EAS) AF: 0.760 AC: 25274 AN: 33234

South Asian (SAS) AF: 0.638 AC: 43629 AN: 68358

European-Finnish (FIN) AF: 0.616 AC: 30193 AN: 49050

Middle Eastern (MID) AF: 0.583 AC: 2214 AN: 3798

European-Non Finnish (NFE) AF: 0.628 AC: 359054 AN: 571832

Other (OTH) AF: 0.646 AC: 25639 AN: 39672

GnomAD4 genome AF: 0.678 AC: 102909 AN: 151750 Hom.: 34930 Cov.: 31 AF XY: 0.676 AC XY: 50123 AN XY: 74158

African (AFR) AF: 0.798 AC: 33057 AN: 41430

American (AMR) AF: 0.656 AC: 9934 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2124 AN: 3466

East Asian (EAS) AF: 0.759 AC: 3905 AN: 5148

South Asian (SAS) AF: 0.627 AC: 3023 AN: 4818

European-Finnish (FIN) AF: 0.623 AC: 6584 AN: 10564

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42249 AN: 67878

Other (OTH) AF: 0.651 AC: 1363 AN: 2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.013
DANN	Benign	0.37
PhyloP100		-4.8
PromoterAI		0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs6644635; hg19: chrX-1733994;