rs8301

Variant names:

• chr11-119024785-C-G
• rs8301
• NM_001164277.2:c.*125G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001164277.2(SLC37A4):​c.*125G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,195,594 control chromosomes in the GnomAD database, including 47,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6461 hom., cov: 32)
  • Exomes 𝑓: 0.27 (40626 hom.)
• Consequence: SLC37A4 NM_001164277.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.177
• Publications: 18 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]

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]

TRAPPC4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-119024785-C-G is Benign according to our data. Variant chr11-119024785-C-G is described in ClinVar as Benign. ClinVar VariationId is 302701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

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.*125G>C		3_prime_UTR	Exon 11 of 11	NP_001157749.1	O43826-1
	SLC37A4	NM_001164278.2		c.*125G>C		3_prime_UTR	Exon 12 of 12	NP_001157750.1	O43826-2
	SLC37A4	NM_001164280.2		c.*125G>C		3_prime_UTR	Exon 9 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.*125G>C		3_prime_UTR	Exon 10 of 10	ENSP00000476242.2	U3KPU7
	SLC37A4	ENST00000526275.5	TSL:1	n.2197G>C		non_coding_transcript_exon	Exon 6 of 6
	SLC37A4	ENST00000527992.5	TSL:1	n.1643G>C		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43418 AN: 151996 Hom.: 6451 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.275 AC: 286477 AN: 1043480 Hom.: 40626 Cov.: 14 AF XY: 0.278 AC XY: 146868 AN XY: 527978

African (AFR) AF: 0.323 AC: 7852 AN: 24322

American (AMR) AF: 0.208 AC: 7272 AN: 34974

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 6614 AN: 22850

East Asian (EAS) AF: 0.156 AC: 5349 AN: 34182

South Asian (SAS) AF: 0.363 AC: 26031 AN: 71666

European-Finnish (FIN) AF: 0.314 AC: 14908 AN: 47470

Middle Eastern (MID) AF: 0.278 AC: 1014 AN: 3642

European-Non Finnish (NFE) AF: 0.270 AC: 204421 AN: 758162

Other (OTH) AF: 0.282 AC: 13016 AN: 46212

GnomAD4 genome AF: 0.286 AC: 43473 AN: 152114 Hom.: 6461 Cov.: 32 AF XY: 0.287 AC XY: 21320 AN XY: 74362

African (AFR) AF: 0.324 AC: 13429 AN: 41494

American (AMR) AF: 0.249 AC: 3808 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3468

East Asian (EAS) AF: 0.150 AC: 778 AN: 5172

South Asian (SAS) AF: 0.378 AC: 1826 AN: 4828

European-Finnish (FIN) AF: 0.330 AC: 3491 AN: 10576

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18348 AN: 67988

Other (OTH) AF: 0.289 AC: 611 AN: 2112

Alfa AF: 0.272 Hom.: 836

Bravo AF: 0.280

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Glycogen storage disease, type I (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.46
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs8301; hg19: chr11-118895495;