rs193302895

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000330775.9(SLC37A4):​c.526T>C​(p.Trp176Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

SLC37A4
ENST00000330775.9 missense, splice_region

Scores

1
3
5

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 6.93

Publications

5 publications found
Variant links:
Genes affected
SLC37A4 (HGNC:4061): (solute carrier family 37 member 4) This gene regulates glucose-6-phosphate transport from the cytoplasm to the lumen of the endoplasmic reticulum, in order to maintain glucose homeostasis. It also plays a role in ATP-mediated calcium sequestration in the lumen of the endoplasmic reticulum. Mutations in this gene have been associated with various forms of glycogen storage disease. Alternative splicing in this gene results in multiple transcript variants.[provided by RefSeq, Aug 2009]
SLC37A4 Gene-Disease associations (from GenCC):
  • congenital disorder of glycosylation, type IIw
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • glycogen storage disease Ib
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
  • glycogen storage disease type 1 due to SLC37A4 mutation
    Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33085793).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC37A4NM_001164278.2 linkc.526T>C p.Cys176Arg missense_variant, splice_region_variant Exon 5 of 12 NP_001157750.1 O43826-2A0A024R3L1
SLC37A4NM_001164277.2 linkc.526T>C p.Cys176Arg missense_variant, splice_region_variant Exon 5 of 11 NP_001157749.1 O43826-1A0A024R3H9A8K0S7
SLC37A4NM_001164280.2 linkc.526T>C p.Cys176Arg missense_variant, splice_region_variant Exon 3 of 9 NP_001157752.1 O43826-1A0A024R3H9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC37A4ENST00000330775.9 linkc.526T>C p.Trp176Arg missense_variant, splice_region_variant Exon 4 of 10 5 ENSP00000476242.2 U3KPU7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
33

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not provided Other:1
-
UniProtKB/Swiss-Prot
Significance:not provided
Review Status:no classification provided
Collection Method:literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Uncertain
0.078
D
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
23
DANN
Benign
0.86
DEOGEN2
Benign
0.11
T;T;T;T
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.39
.;T;T;T
MetaRNN
Benign
0.33
T;T;T;T
PhyloP100
6.9
Sift4G
Uncertain
0.0080
D;D;D;D
Vest4
0.41
MVP
0.61
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
gMVP
0.94
Mutation Taster
=0/100
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs193302895; hg19: chr11-118898438; API