rs1250300189

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PS1_ModeratePM2

The NM_000199.5(SGSH):​c.1A>T​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000747 in 1,339,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

SGSH
NM_000199.5 start_lost

Scores

5
4
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0990
Variant links:
Genes affected
SGSH (HGNC:10818): (N-sulfoglucosamine sulfohydrolase) This gene encodes the enzyme sulfamidase; one of several enzymes involved in the lysosomal degradation of heparan sulfate. Mutations in this gene are associated with the lysosomal storage disease mucopolysaccaridosis IIIA, also known as Sanfilippo syndrome A, which results from impaired degradation of heparan sulfate. Transcripts of varying sizes have been reported but their biological validity has not been determined. [provided by RefSeq, Jun 2017]
SLC26A11 (HGNC:14471): (solute carrier family 26 member 11) This gene encodes a member of the solute linked carrier 26 family of anion exchangers. Members of this family of proteins are essential for numerous cellular functions including homeostasis and intracellular electrolyte balance. The encoded protein is a sodium independent sulfate transporter that is sensitive to the anion exchanger inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Start lost variant, no new inframe start found.
PS1
Another start lost variant in NM_000199.5 (SGSH) was described as [Pathogenic] in Lovd
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SGSHNM_000199.5 linkuse as main transcriptc.1A>T p.Met1? start_lost 1/8 ENST00000326317.11 NP_000190.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SGSHENST00000326317.11 linkuse as main transcriptc.1A>T p.Met1? start_lost 1/81 NM_000199.5 ENSP00000314606 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.47e-7
AC:
1
AN:
1339210
Hom.:
0
Cov.:
31
AF XY:
0.00000152
AC XY:
1
AN XY:
659624
show subpopulations
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:
9.44e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.50
D
BayesDel_noAF
Pathogenic
0.48
CADD
Benign
16
DANN
Benign
0.69
DEOGEN2
Benign
0.084
T;.;.
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.58
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Pathogenic
0.97
D
MetaRNN
Pathogenic
0.97
D;D;D
MetaSVM
Uncertain
0.42
D
MutationTaster
Benign
1.0
D;D;D
PROVEAN
Benign
-0.24
N;.;.
REVEL
Uncertain
0.63
Sift
Pathogenic
0.0
D;.;.
Sift4G
Benign
0.78
T;D;.
Polyphen
0.0040
B;.;.
Vest4
0.79
MutPred
0.91
Loss of catalytic residue at M1 (P = 0.1238);Loss of catalytic residue at M1 (P = 0.1238);Loss of catalytic residue at M1 (P = 0.1238);
MVP
0.88
ClinPred
0.84
D
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.0
Varity_R
0.93
gMVP
0.55

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1250300189; hg19: chr17-78194112; API