rs193302894

Variant names:

• chr11-119029222-C-G
• rs193302894
• ENST00000330775.9:c.148G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-119029222-C-G
• chr11-119029222-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM5 PP3_Moderate

The NM_001164278.2(SLC37A4):​c.148G>C​(p.Gly50Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G50E) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC37A4 NM_001164278.2 missense, splice_region
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 7.06

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr11-119028426-C-T is described in Lovd as [Pathogenic].
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC37A4	NM_001164278.2	c.148G>C	p.Gly50Arg	missense_variant, splice_region_variant	Exon 3 of 12		NP_001157750.1
SLC37A4	NM_001164277.2	c.148G>C	p.Gly50Arg	missense_variant, splice_region_variant	Exon 3 of 11		NP_001157749.1
SLC37A4	NM_001164280.2	c.148G>C	p.Gly50Arg	missense_variant, splice_region_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.148G>C	p.Gly50Arg	missense_variant, splice_region_variant	Exon 2 of 10	5		ENSP00000476242.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

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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	0.99
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	32
DANN	Benign	0.97
DEOGEN2	Uncertain	0.64	D;D;D
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	.;D;D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.93	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		1.0
MVP		0.57
MPC		0.23
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.43		Position offset: 0

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

Publications

LitVar

Other links and lift over

dbSNP: rs193302894; hg19: chr11-118899932;