11-119024492-A-G

Variant names:

• chr11-119024492-A-G
• rs11006
• NM_001164277.2:c.*418T>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.*418T>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 0.191 in 249,338 control chromosomes in the GnomAD database, including 5,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3024 hom., cov: 32)
  • Exomes 𝑓: 0.19 (2095 hom.)
• Consequence: SLC37A4 NM_001164277.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.290
• Publications: 28 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=-0.87).
• BP6: Variant 11-119024492-A-G is Benign according to our data. Variant chr11-119024492-A-G is described in ClinVar as Benign. ClinVar VariationId is 302695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 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.*418T>C		3_prime_UTR	Exon 11 of 11	NP_001157749.1	O43826-1
	SLC37A4	NM_001164278.2		c.*418T>C		3_prime_UTR	Exon 12 of 12	NP_001157750.1	O43826-2
	SLC37A4	NM_001164280.2		c.*418T>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.*418T>C		3_prime_UTR	Exon 10 of 10	ENSP00000476242.2	U3KPU7
	SLC37A4	ENST00000526275.5	TSL:1	n.2490T>C		non_coding_transcript_exon	Exon 6 of 6
	SLC37A4	ENST00000527992.5	TSL:1	n.1936T>C		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28977 AN: 151974 Hom.: 3021 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.191 AC: 18618 AN: 97246 Hom.: 2095 Cov.: 0 AF XY: 0.200 AC XY: 10184 AN XY: 50992

African (AFR) AF: 0.112 AC: 392 AN: 3502

American (AMR) AF: 0.164 AC: 745 AN: 4544

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 455 AN: 2662

East Asian (EAS) AF: 0.0879 AC: 499 AN: 5680

South Asian (SAS) AF: 0.264 AC: 3130 AN: 11846

European-Finnish (FIN) AF: 0.201 AC: 804 AN: 4004

Middle Eastern (MID) AF: 0.184 AC: 71 AN: 386

European-Non Finnish (NFE) AF: 0.195 AC: 11544 AN: 59328

Other (OTH) AF: 0.185 AC: 978 AN: 5294

GnomAD4 genome AF: 0.191 AC: 28992 AN: 152092 Hom.: 3024 Cov.: 32 AF XY: 0.192 AC XY: 14261 AN XY: 74348

African (AFR) AF: 0.128 AC: 5327 AN: 41492

American (AMR) AF: 0.188 AC: 2876 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3472

East Asian (EAS) AF: 0.0913 AC: 472 AN: 5170

South Asian (SAS) AF: 0.325 AC: 1560 AN: 4802

European-Finnish (FIN) AF: 0.251 AC: 2653 AN: 10580

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14870 AN: 67990

Other (OTH) AF: 0.205 AC: 434 AN: 2112

Alfa AF: 0.203 Hom.: 5630

Bravo AF: 0.180

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.53
PhyloP100		0.29
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: rs11006; hg19: chr11-118895202;