rs61730035

Variant names:

• chr11-119025252-G-A
• rs61730035
• NM_001164277.2:c.1062C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-119025252-G-A
• chr11-119025252-G-C
• chr11-119025252-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001164277.2(SLC37A4):​c.1062C>T​(p.Asn354Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,613,168 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (10 hom., cov: 33)
  • Exomes 𝑓: 0.012 (135 hom.)
• Consequence: SLC37A4 NM_001164277.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.310
• Publications: 6 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 11-119025252-G-A is Benign according to our data. Variant chr11-119025252-G-A is described in ClinVar as Benign. ClinVar VariationId is 139191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.31 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00927 (1412/152372) while in subpopulation AMR AF = 0.016 (245/15308). AF 95% confidence interval is 0.0144. There are 10 homozygotes in GnomAd4. There are 659 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR,AD gene

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.1062C>T	p.Asn354Asn	synonymous	Exon 10 of 11	NP_001157749.1	O43826-1
	SLC37A4	NM_001164278.2		c.1128C>T	p.Asn376Asn	synonymous	Exon 11 of 12	NP_001157750.1	O43826-2
	SLC37A4	NM_001164280.2		c.1062C>T	p.Asn354Asn	synonymous	Exon 8 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.1062C>T	p.Asn354Asn	synonymous	Exon 9 of 10	ENSP00000476242.2	U3KPU7
	SLC37A4	ENST00000524428.5	TSL:1	n.1298C>T		non_coding_transcript_exon	Exon 5 of 6
	SLC37A4	ENST00000525039.5	TSL:1	n.1552C>T		non_coding_transcript_exon	Exon 10 of 11

Frequencies

GnomAD3 genomes AF: 0.00927 AC: 1412 AN: 152254 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00928 AC: 2291 AN: 246964 AF XY: 0.00979

Gnomad AFR exome AF: 0.00255

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0154

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00238

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.0159

GnomAD4 exome AF: 0.0116 AC: 16940 AN: 1460796 Hom.: 135 Cov.: 34 AF XY: 0.0115 AC XY: 8326 AN XY: 726618

African (AFR) AF: 0.00341 AC: 114 AN: 33466

American (AMR) AF: 0.0113 AC: 504 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.0151 AC: 394 AN: 26110

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39664

South Asian (SAS) AF: 0.00268 AC: 231 AN: 86104

European-Finnish (FIN) AF: 0.00281 AC: 150 AN: 53312

Middle Eastern (MID) AF: 0.0338 AC: 195 AN: 5766

European-Non Finnish (NFE) AF: 0.0131 AC: 14612 AN: 1111484

Other (OTH) AF: 0.0122 AC: 739 AN: 60344

GnomAD4 genome AF: 0.00927 AC: 1412 AN: 152372 Hom.: 10 Cov.: 33 AF XY: 0.00884 AC XY: 659 AN XY: 74508

African (AFR) AF: 0.00351 AC: 146 AN: 41592

American (AMR) AF: 0.0160 AC: 245 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10622

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0133 AC: 902 AN: 68042

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.0126 Hom.: 49

Bravo AF: 0.00966

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	4	not specified (4)
-	-	2	Glucose-6-phosphate transport defect (2)
-	-	1	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA (1)
-	-	1	Phosphate transport defect (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		-0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=88/12	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: rs61730035; hg19: chr11-118895962; COSMIC: COSV58155288; COSMIC: COSV58155288;