ENST00000651111.1:c.-169T>G

Variant names:

• chrX-149500991-A-C
• ENST00000651111.1:c.-169T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000651111.1(ENSG00000241489):​c.-169T>G variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: ENSG00000241489 ENST00000651111.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 0 publications found

Genes affected

ENSG00000241489 (HGNC:):

IDS (HGNC:5389): (iduronate 2-sulfatase) This gene encodes a member of the sulfatase family of proteins. The encoded preproprotein is proteolytically processed to generate two polypeptide chains. This enzyme is involved in the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations in this gene are associated with the X-linked lysosomal storage disease mucopolysaccharidosis type II, also known as Hunter syndrome. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

IDS Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 2

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Myriad Women's Health, ClinGen, Labcorp Genetics (formerly Invitae)
• mucopolysaccharidosis type 2, attenuated form

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• mucopolysaccharidosis type 2, severe form

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08145434).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651111.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDS	NM_000202.8	MANE Select	c.465T>G	p.Phe155Leu	missense	Exon 4 of 9	NP_000193.1	P22304-1
	IDS	NM_001166550.4		c.195T>G	p.Phe65Leu	missense	Exon 4 of 9	NP_001160022.1	B4DGD7
	IDS	NM_006123.5		c.465T>G	p.Phe155Leu	missense	Exon 4 of 8	NP_006114.1	P22304-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000241489	ENST00000651111.1		c.-169T>G		5_prime_UTR_premature_start_codon_gain	Exon 9 of 14	ENSP00000498395.1	B3KWA1
	IDS	ENST00000340855.11	TSL:1 MANE Select	c.465T>G	p.Phe155Leu	missense	Exon 4 of 9	ENSP00000339801.6	P22304-1
	IDS	ENST00000370441.8	TSL:1	c.465T>G	p.Phe155Leu	missense	Exon 4 of 8	ENSP00000359470.4	P22304-2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.0011	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	6.8
DANN	Benign	0.71
DEOGEN2	Uncertain	0.60	D
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.081	T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	-0.97	N
PhyloP100		0.12
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.27	N
REVEL	Uncertain	0.33
Sift	Benign	0.70	T
Sift4G	Benign	0.68	T
Varity_R		0.18
gMVP		0.88
Mutation Taster		=297/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-148582522;