chr11-119025251-C-G

Variant names:

• chr11-119025251-C-G
• ENST00000330775.9:c.1063G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_001164278.2(SLC37A4):​c.1129G>C​(p.Glu377Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,928 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: 6.8e-7 (0 hom.)
• Consequence: SLC37A4 NM_001164278.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.37

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a transmembrane_region Helical (size 20) in uniprot entity G6PT1_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_001164278.2
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC37A4	NM_001164278.2	c.1129G>C	p.Glu377Gln	missense_variant	Exon 11 of 12		NP_001157750.1
SLC37A4	NM_001164277.2	c.1063G>C	p.Glu355Gln	missense_variant	Exon 10 of 11		NP_001157749.1
SLC37A4	NM_001164280.2	c.1063G>C	p.Glu355Gln	missense_variant	Exon 8 of 9		NP_001157752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC37A4	ENST00000330775.9	c.1063G>C	p.Glu355Gln	missense_variant	Exon 9 of 10	5		ENSP00000476242.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460928 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726692

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: 9.00e-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
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	28
DANN	Benign	0.93
DEOGEN2	Benign	0.40	T;T;T;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	.;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.86	D;D;D;D
PrimateAI	Uncertain	0.72	T
Sift4G	Uncertain	0.0080	D;D;D;D
Vest4		0.92
MVP		0.39
MPC		0.21
GERP RS		5.1
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-118895961;