11-119027762-G-A

Variant names:

• chr11-119027762-G-A
• rs369399624
• NM_001164277.2:c.492C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001164277.2(SLC37A4):​c.492C>T​(p.Ser164Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,612,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: SLC37A4 NM_001164277.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: 2.55
• Publications: 1 publications found

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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• glycogen storage disease Ib

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• glycogen storage disease type 1 due to SLC37A4 mutation

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 11-119027762-G-A is Benign according to our data. Variant chr11-119027762-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 302706.
• BP7: Synonymous conserved (PhyloP=2.55 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164277.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC37A4	NM_001164277.2	MANE Select	c.492C>T	p.Ser164Ser	synonymous	Exon 5 of 11	NP_001157749.1	O43826-1
	SLC37A4	NM_001164278.2		c.492C>T	p.Ser164Ser	synonymous	Exon 5 of 12	NP_001157750.1	O43826-2
	SLC37A4	NM_001164280.2		c.492C>T	p.Ser164Ser	synonymous	Exon 3 of 9	NP_001157752.1	O43826-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC37A4	ENST00000330775.9	TSL:5	c.492C>T	p.Ser164Ser	synonymous	Exon 4 of 10	ENSP00000476242.2	U3KPU7
	SLC37A4	ENST00000524428.5	TSL:1	n.813C>T		non_coding_transcript_exon	Exon 2 of 6
	SLC37A4	ENST00000525039.5	TSL:1	n.915C>T		non_coding_transcript_exon	Exon 5 of 11

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152266 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000689 AC: 17 AN: 246696 AF XY: 0.0000374

Gnomad AFR exome AF: 0.0000655

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000155 AC: 227 AN: 1460496 Hom.: 0 Cov.: 35 AF XY: 0.000153 AC XY: 111 AN XY: 726438

African (AFR) AF: 0.0000299 AC: 1 AN: 33452

American (AMR) AF: 0.0000674 AC: 3 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000194 AC: 216 AN: 1111244

Other (OTH) AF: 0.000116 AC: 7 AN: 60338

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74396

African (AFR) AF: 0.0000482 AC: 2 AN: 41480

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000982

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	Glucose-6-phosphate transport defect (1)
-	-	1	Glucose-6-phosphate transport defect;C0342749:Phosphate transport defect;C5561986:Congenital disorder of glycosylation, type IIw (1)
-	1	-	Glycogen storage disease, type I (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Benign	0.84
PhyloP100		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs369399624; hg19: chr11-118898472;