NM_001171038.2:c.646+44C>T

Variant names:

• chrX-1632831-C-T
• rs7471973
• NM_001171038.2:c.646+44C>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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28189 AN: 150828 Hom.: 2587 Cov.: 30

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

GnomAD2 exomes AF: 0.180 AC: 9832 AN: 54638 AF XY: 0.183

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 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.: 0 AF XY: 0.199 AC XY: 34328 AN XY: 172784

African (AFR) AF: 0.163 AC: 1638 AN: 10028

American (AMR) AF: 0.164 AC: 2452 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 2570 AN: 9902

East Asian (EAS) AF: 0.0636 AC: 1268 AN: 19938

South Asian (SAS) AF: 0.203 AC: 8433 AN: 41630

European-Finnish (FIN) AF: 0.132 AC: 2371 AN: 17936

Middle Eastern (MID) AF: 0.238 AC: 341 AN: 1434

European-Non Finnish (NFE) AF: 0.217 AC: 42218 AN: 194250

Other (OTH) AF: 0.202 AC: 3817 AN: 18880

GnomAD4 genome AF: 0.187 AC: 28191 AN: 150944 Hom.: 2589 Cov.: 30 AF XY: 0.182 AC XY: 13431 AN XY: 73668

African (AFR) AF: 0.167 AC: 6863 AN: 41044

American (AMR) AF: 0.177 AC: 2663 AN: 15080

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 876 AN: 3458

East Asian (EAS) AF: 0.0569 AC: 292 AN: 5128

South Asian (SAS) AF: 0.206 AC: 982 AN: 4758

European-Finnish (FIN) AF: 0.113 AC: 1179 AN: 10408

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.216 AC: 14656 AN: 67774

Other (OTH) AF: 0.227 AC: 474 AN: 2092

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
PhyloP100		0.11

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

Other links and lift over

dbSNP: rs7471973; hg19: chrX-1751724;