rs34203644

Variant names:

• chr11-119027660-T-A
• rs34203644
• NM_001164277.2:c.593A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-119027660-T-A
• chr11-119027660-T-C
• chr11-119027660-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001164278.2(SLC37A4):​c.593A>T​(p.Asn198Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00492 in 1,613,926 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N198S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0039 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (23 hom.)
• Consequence: SLC37A4 NM_001164278.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 3.77
• Publications: 9 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: G2P, Labcorp Genetics (formerly Invitae)
• glycogen storage disease Ib

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, PanelApp Australia, 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015274823).
• BP6: Variant 11-119027660-T-A is Benign according to our data. Variant chr11-119027660-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00387 (590/152306) while in subpopulation AMR AF = 0.00797 (122/15298). AF 95% confidence interval is 0.00682. There are 4 homozygotes in GnomAd4. There are 275 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164278.2. 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.593A>T	p.Asn198Ile	missense	Exon 6 of 11	NP_001157749.1
	SLC37A4	NM_001164278.2		c.593A>T	p.Asn198Ile	missense	Exon 6 of 12	NP_001157750.1
	SLC37A4	NM_001164280.2		c.593A>T	p.Asn198Ile	missense	Exon 4 of 9	NP_001157752.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC37A4	ENST00000330775.9	TSL:5	c.593A>T	p.Asn198Ile	missense	Exon 5 of 10	ENSP00000476242.2
	SLC37A4	ENST00000524428.5	TSL:1	n.915A>T		non_coding_transcript_exon	Exon 2 of 6
	SLC37A4	ENST00000525039.5	TSL:1	n.1017A>T		non_coding_transcript_exon	Exon 5 of 11

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 590 AN: 152188 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00572

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00363 AC: 903 AN: 249060 AF XY: 0.00366

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.00493

Gnomad ASJ exome AF: 0.00368

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000789

Gnomad NFE exome AF: 0.00549

Gnomad OTH exome AF: 0.00579

GnomAD4 exome AF: 0.00503 AC: 7349 AN: 1461620 Hom.: 23 Cov.: 32 AF XY: 0.00493 AC XY: 3581 AN XY: 727092

African (AFR) AF: 0.000866 AC: 29 AN: 33480

American (AMR) AF: 0.00523 AC: 234 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00329 AC: 86 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86218

European-Finnish (FIN) AF: 0.00120 AC: 64 AN: 53402

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00595 AC: 6614 AN: 1111840

Other (OTH) AF: 0.00490 AC: 296 AN: 60374

GnomAD4 genome AF: 0.00387 AC: 590 AN: 152306 Hom.: 4 Cov.: 33 AF XY: 0.00369 AC XY: 275 AN XY: 74492

African (AFR) AF: 0.00108 AC: 45 AN: 41564

American (AMR) AF: 0.00797 AC: 122 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00572 AC: 389 AN: 68018

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00477 Hom.: 4

Bravo AF: 0.00396

TwinsUK AF: 0.00485 AC: 18

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00120 AC: 5

ESP6500EA AF: 0.00618 AC: 52

ExAC AF: 0.00363 AC: 439

EpiCase AF: 0.00649

EpiControl AF: 0.00711

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not provided (8)
-	-	2	Glucose-6-phosphate transport defect (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Pathogenic	0.17
CADD	Benign	23
DANN	Benign	0.85
DEOGEN2	Benign	0.40	T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.015	T
PhyloP100		3.8
PrimateAI	Uncertain	0.55	T
Sift4G	Uncertain	0.012	D
Vest4		0.75
MVP		0.58
MPC		0.088
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.73
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34203644; hg19: chr11-118898370;