rs6588809

Positions:

• chrX-1632709-T-A
• chrX-1632709-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001171038.2(ASMT):​c.568T>A​(p.Trp190Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ASMT NM_001171038.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1325694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.568T>A	p.Trp190Arg	missense_variant	6/9	ENST00000381241.9	NP_001164509.1
ASMT	NM_001171039.1	c.562+2770T>A		intron_variant			NP_001164510.1
ASMT	NM_001416525.1	c.563-441T>A		intron_variant			NP_001403454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.568T>A	p.Trp190Arg	missense_variant	6/9	1	NM_001171038.2	ENSP00000370639
ASMT	ENST00000381229.9	c.563-441T>A		intron_variant		1		ENSP00000370627	P1
ASMT	ENST00000381233.8	c.562+2770T>A		intron_variant		1		ENSP00000370631
ASMT	ENST00000509780.6	n.289-3533T>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 92688 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 48498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.2
DANN	Benign	0.90
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.87	T
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.029
Sift	Benign	0.28	T
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.61		Gain of solvent accessibility (P = 0.0584);
MVP		0.12
MPC		0.025
ClinPred		0.094	T

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

Publications

LitVar

Other links and lift over

dbSNP: rs6588809; hg19: chrX-1751602;