X-1624390-C-G

Variant names:

• chrX-1624390-C-G
• NM_001171038.2:c.366C>G

Variant summary

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

The NM_001171038.2(ASMT):​c.366C>G​(p.Asp122Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,070 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom. 1 hem.)
• Consequence: ASMT NM_001171038.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASMT	NM_001171038.2	c.366C>G	p.Asp122Glu	missense_variant	Exon 3 of 9	ENST00000381241.9	NP_001164509.1
ASMT	NM_001416525.1	c.366C>G	p.Asp122Glu	missense_variant	Exon 3 of 8		NP_001403454.1
ASMT	NM_001171039.1	c.366C>G	p.Asp122Glu	missense_variant	Exon 3 of 7		NP_001164510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASMT	ENST00000381241.9	c.366C>G	p.Asp122Glu	missense_variant	Exon 3 of 9	1	NM_001171038.2	ENSP00000370639.3
ASMT	ENST00000381229.9	c.366C>G	p.Asp122Glu	missense_variant	Exon 3 of 8	1		ENSP00000370627.4
ASMT	ENST00000381233.8	c.366C>G	p.Asp122Glu	missense_variant	Exon 3 of 7	1		ENSP00000370631.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461070 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726838

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: 0.00000180

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	-0.55	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.20
DEOGEN2	Benign	0.0029	.;T;.
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.074	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.93	N;N;N
REVEL	Benign	0.043
Sift	Benign	0.84	T;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.039	B;.;B
Vest4		0.21
MutPred		0.56		Loss of MoRF binding (P = 0.1161);Loss of MoRF binding (P = 0.1161);Loss of MoRF binding (P = 0.1161);
MVP		0.36
MPC		0.022
ClinPred		0.045	T
GERP RS		-1.5
Varity_R		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-1743283;