rs786204740

Variant names:

• chr11-119029369-T-A
• ENST00000330775.9:c.1A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-119029369-T-A
• chr11-119029369-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_001164278.2(SLC37A4):​c.1A>T​(p.Met1?) variant causes a initiator codon change. The variant allele was found at a frequency of 0.00000206 in 1,459,112 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: 0.0000021 (0 hom.)
• Consequence: SLC37A4 NM_001164278.2 initiator_codon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.14

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 17 codons. Genomic position: 119029321. Lost 0.036 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC37A4	NM_001164278.2	c.1A>T	p.Met1?	initiator_codon_variant	Exon 3 of 12		NP_001157750.1
SLC37A4	NM_001164277.2	c.1A>T	p.Met1?	initiator_codon_variant	Exon 3 of 11		NP_001157749.1
SLC37A4	NM_001164280.2	c.1A>T	p.Met1?	initiator_codon_variant	Exon 1 of 9		NP_001157752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC37A4	ENST00000330775.9	c.1A>T	p.Met1?	initiator_codon_variant	Exon 2 of 10	5		ENSP00000476242.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459112 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725828

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: 0.00000270

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	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Uncertain	24
DANN	Benign	0.71
DEOGEN2	Benign	0.021	T;T;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.80	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.85
MVP		0.42
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.31		Position offset: -7

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: chr11-118900079;