11-119024841-CCTT-C

Variant summary

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

The ENST00000330775.9(SLC37A4):​c.*66_*68del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000645 in 1,550,158 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

SLC37A4
ENST00000330775.9 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0830
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]
TRAPPC4 (HGNC:19943): (trafficking protein particle complex subunit 4) Involved in autophagy and endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons MANE UniProt
SLC37A4NM_001164277.2 linkuse as main transcriptc.*66_*68del 3_prime_UTR_variant 11/11 ENST00000642844.3
SLC37A4NM_001164279.2 linkuse as main transcriptc.*66_*68del 3_prime_UTR_variant 11/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC37A4ENST00000330775.9 linkuse as main transcriptc.*66_*68del 3_prime_UTR_variant 10/105 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152248
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000509
AC:
1
AN:
196430
Hom.:
0
AF XY:
0.00000946
AC XY:
1
AN XY:
105662
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000117
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000429
AC:
6
AN:
1397910
Hom.:
0
AF XY:
0.00000288
AC XY:
2
AN XY:
694162
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:
0.00000468
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152248
Hom.:
1
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000567

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpJul 15, 2022Variant summary: SLC37A4 c.*66_*68delAAG is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 5.1e-06 in 196430 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.*66_*68delAAG in individuals affected with Glycogen Storage Disease Type Ib and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs782551469; hg19: chr11-118895551; API