rs78952091

Variant names:

• chr2-69354499-G-A
• rs78952091
• NM_001244710.2:c.675C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-69354499-G-A
• chr2-69354499-G-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001244710.2(GFPT1):​c.675C>T​(p.Leu225Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,584,282 control chromosomes in the GnomAD database, including 1,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (128 hom., cov: 33)
  • Exomes 𝑓: 0.014 (1257 hom.)
• Consequence: GFPT1 NM_001244710.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.33
• Publications: 10 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), Ambry Genetics, ClinGen, Illumina
• congenital myasthenic syndromes with glycosylation defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 2-69354499-G-A is Benign according to our data. Variant chr2-69354499-G-A is described in ClinVar as Benign. ClinVar VariationId is 129153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244710.2. 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
	GFPT1	NM_001244710.2	MANE Select	c.675C>T	p.Leu225Leu	synonymous	Exon 8 of 20	NP_001231639.1	Q06210-1
	GFPT1	NM_002056.4		c.675C>T	p.Leu225Leu	synonymous	Exon 8 of 19	NP_002047.2	Q06210-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFPT1	ENST00000357308.9	TSL:5 MANE Select	c.675C>T	p.Leu225Leu	synonymous	Exon 8 of 20	ENSP00000349860.4	Q06210-1
	GFPT1	ENST00000361060.5	TSL:1	c.675C>T	p.Leu225Leu	synonymous	Exon 8 of 19	ENSP00000354347.4	Q06210-2
	GFPT1	ENST00000955842.1		c.723C>T	p.Leu241Leu	synonymous	Exon 9 of 21	ENSP00000625901.1

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2237 AN: 152092 Hom.: 128 Cov.: 33

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.0168

GnomAD2 exomes AF: 0.0285 AC: 7152 AN: 251134 AF XY: 0.0306

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.186

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.00208

Gnomad OTH exome AF: 0.0145

GnomAD4 exome AF: 0.0137 AC: 19607 AN: 1432072 Hom.: 1257 Cov.: 26 AF XY: 0.0160 AC XY: 11420 AN XY: 714372

African (AFR) AF: 0.0135 AC: 443 AN: 32920

American (AMR) AF: 0.00186 AC: 83 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00505 AC: 131 AN: 25932

East Asian (EAS) AF: 0.188 AC: 7417 AN: 39494

South Asian (SAS) AF: 0.0937 AC: 8019 AN: 85600

European-Finnish (FIN) AF: 0.000731 AC: 39 AN: 53374

Middle Eastern (MID) AF: 0.00947 AC: 54 AN: 5702

European-Non Finnish (NFE) AF: 0.00198 AC: 2145 AN: 1085052

Other (OTH) AF: 0.0215 AC: 1276 AN: 59306

GnomAD4 genome AF: 0.0147 AC: 2234 AN: 152210 Hom.: 128 Cov.: 33 AF XY: 0.0169 AC XY: 1259 AN XY: 74404

African (AFR) AF: 0.0127 AC: 526 AN: 41520

American (AMR) AF: 0.00497 AC: 76 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.184 AC: 952 AN: 5178

South Asian (SAS) AF: 0.0971 AC: 468 AN: 4818

European-Finnish (FIN) AF: 0.000378 AC: 4 AN: 10586

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00232 AC: 158 AN: 68036

Other (OTH) AF: 0.0166 AC: 35 AN: 2110

Alfa AF: 0.00525 Hom.: 16

Bravo AF: 0.0140

Asia WGS AF: 0.127 AC: 442 AN: 3478

EpiCase AF: 0.00229

EpiControl AF: 0.00267

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Congenital myasthenic syndrome 12 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.5
DANN	Benign	0.70
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.24		Position offset: -10

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs78952091; hg19: chr2-69581631; COSMIC: COSV61947795;