rs10794537

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_000203.5(IDUA):c.99T>A(p.His33Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,321,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

Frequency

Genomes: not found (cov: 38)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

IDUA
NM_000203.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.44

Publications

0 publications found

Variant links:

Genes affected

IDUA (HGNC:5391): (alpha-L-iduronidase) This gene encodes an enzyme that hydrolyzes the terminal alpha-L-iduronic acid residues of two glycosaminoglycans, dermatan sulfate and heparan sulfate. This hydrolysis is required for the lysosomal degradation of these glycosaminoglycans. Mutations in this gene that result in enzymatic deficiency lead to the autosomal recessive disease mucopolysaccharidosis type I (MPS I). [provided by RefSeq, Jul 2008]

IDUA links:

SLC26A1 (HGNC:10993): (solute carrier family 26 member 1) This gene is a member of a family of sulfate/anion transporter genes. Family members are well conserved in their genomic (number and size of exons) and protein (aa length among species) structures, but have markedly different tissue expression patterns. This gene is primarily expressed in the liver, pancreas, and brain. Three splice variants that encode different isoforms have been identified. [provided by RefSeq, Jul 2008]

SLC26A1 Gene-Disease associations (from GenCC):

nephrolithiasis susceptibility caused by SLC26A1
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

SLC26A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24450672).

BP6

Variant 4-987183-T-A is Benign according to our data. Variant chr4-987183-T-A is described in ClinVar as Benign. ClinVar VariationId is 2134405.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDUA	NM_000203.5 link	c.99T>A	p.His33Gln	missense_variant	Exon 1 of 14	ENST00000514224.2	NP_000194.2	P35475-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDUA	ENST00000514224.2 link	c.99T>A	p.His33Gln	missense_variant	Exon 1 of 14	2	NM_000203.5	ENSP00000425081.2		P35475-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.57e-7

AC:

AN:

1321296

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

651284

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26630

American (AMR)

AF:

0.00

AC:

AN:

27900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23200

East Asian (EAS)

AF:

0.00

AC:

AN:

28562

South Asian (SAS)

AF:

0.00

AC:

AN:

72678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3894

European-Non Finnish (NFE)

AF:

9.52e-7

AC:

AN:

1050822

Other (OTH)

AF:

0.00

AC:

AN:

54706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mucopolysaccharidosis type 1

Benign:1

May 05, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

0.30

(source)

DANN

Benign

0.77

DEOGEN2

Uncertain

0.45

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.041

T;T

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

-0.69

N;.

PhyloP100

-2.4

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.75

N;N

REVEL

Uncertain

0.37

Sift

Benign

0.46

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0

B;.

Vest4

0.011

MutPred

0.40

Gain of MoRF binding (P = 0.1031);Gain of MoRF binding (P = 0.1031);

MVP

0.55

MPC

0.19

ClinPred

0.044

GERP RS

-0.90

PromoterAI

0.084

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.10

gMVP

0.40

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over