rs2230300

Variant names:

• chr2-69370077-A-G
• rs2230300
• NM_001244710.2:c.147T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-69370077-A-G
• chr2-69370077-A-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 ENST00000357308.9(GFPT1):​c.147T>C​(p.Asp49Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,610,460 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (35 hom., cov: 32)
  • Exomes 𝑓: 0.020 (396 hom.)
• Consequence: GFPT1 ENST00000357308.9 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.441
• Publications: 5 publications found

Genes affected

GFPT1 (HGNC:4241): (glutamine--fructose-6-phosphate transaminase 1) This gene encodes the first and rate-limiting enzyme of the hexosamine pathway and controls the flux of glucose into the hexosamine pathway. The product of this gene catalyzes the formation of glucosamine 6-phosphate. [provided by RefSeq, Sep 2008]

GFPT1 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 12

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, Illumina
• congenital myasthenic syndromes with glycosylation defect

  Inheritance: AR 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=-0.56).
• BP6: Variant 2-69370077-A-G is Benign according to our data. Variant chr2-69370077-A-G is described in ClinVar as Benign. ClinVar VariationId is 129152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.441 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0162 (2474/152296) while in subpopulation NFE AF = 0.0248 (1690/68024). AF 95% confidence interval is 0.0239. There are 35 homozygotes in GnomAd4. There are 1172 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000357308.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFPT1	NM_001244710.2	MANE Select	c.147T>C	p.Asp49Asp	synonymous	Exon 3 of 20	NP_001231639.1
	GFPT1	NM_002056.4		c.147T>C	p.Asp49Asp	synonymous	Exon 3 of 19	NP_002047.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFPT1	ENST00000357308.9	TSL:5 MANE Select	c.147T>C	p.Asp49Asp	synonymous	Exon 3 of 20	ENSP00000349860.4
	GFPT1	ENST00000361060.5	TSL:1	c.147T>C	p.Asp49Asp	synonymous	Exon 3 of 19	ENSP00000354347.4
	GFPT1	ENST00000674507.1		c.147T>C	p.Asp49Asp	synonymous	Exon 3 of 18	ENSP00000501332.1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2471 AN: 152178 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.00451

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.0162 AC: 4083 AN: 251410 AF XY: 0.0167

Gnomad AFR exome AF: 0.00425

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0231

Gnomad NFE exome AF: 0.0250

Gnomad OTH exome AF: 0.0201

GnomAD4 exome AF: 0.0205 AC: 29836 AN: 1458164 Hom.: 396 Cov.: 29 AF XY: 0.0202 AC XY: 14643 AN XY: 725622

African (AFR) AF: 0.00338 AC: 113 AN: 33422

American (AMR) AF: 0.0132 AC: 592 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00295 AC: 77 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39648

South Asian (SAS) AF: 0.00337 AC: 290 AN: 86178

European-Finnish (FIN) AF: 0.0226 AC: 1207 AN: 53394

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5758

European-Non Finnish (NFE) AF: 0.0239 AC: 26503 AN: 1108658

Other (OTH) AF: 0.0173 AC: 1043 AN: 60276

GnomAD4 genome AF: 0.0162 AC: 2474 AN: 152296 Hom.: 35 Cov.: 32 AF XY: 0.0157 AC XY: 1172 AN XY: 74468

African (AFR) AF: 0.00450 AC: 187 AN: 41572

American (AMR) AF: 0.0163 AC: 249 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4822

European-Finnish (FIN) AF: 0.0263 AC: 279 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0248 AC: 1690 AN: 68024

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.0191 Hom.: 103

Bravo AF: 0.0154

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.0231

EpiControl AF: 0.0232

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Congenital myasthenic syndrome 12 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.8
DANN	Benign	0.63
PhyloP100		-0.44
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs2230300; hg19: chr2-69597209;