NM_001244710.2:c.*6085C>G

Variant names:

• chr2-69320104-G-C
• rs7642
• NM_001244710.2:c.*6085C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001244710.2(GFPT1):​c.*6085C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,056 control chromosomes in the GnomAD database, including 34,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (34359 hom., cov: 32)
  • Exomes 𝑓: 0.67 (2 hom.)
• Consequence: GFPT1 NM_001244710.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.810
• Publications: 7 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: Ambry Genetics, ClinGen, Genomics England PanelApp, PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae)
• congenital myasthenic syndromes with glycosylation defect

  Inheritance: AR 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=-0.95).
• BP6: Variant 2-69320104-G-C is Benign according to our data. Variant chr2-69320104-G-C is described in ClinVar as Benign. ClinVar VariationId is 336784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 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.*6085C>G		3_prime_UTR	Exon 20 of 20	NP_001231639.1	Q06210-1
	GFPT1	NM_002056.4		c.*6085C>G		3_prime_UTR	Exon 19 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.*6085C>G		3_prime_UTR	Exon 20 of 20	ENSP00000349860.4	Q06210-1
	GFPT1	ENST00000361060.5	TSL:1	c.*6085C>G		3_prime_UTR	Exon 19 of 19	ENSP00000354347.4	Q06210-2

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99955 AN: 151932 Hom.: 34317 Cov.: 32

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.658 AC: 100052 AN: 152050 Hom.: 34359 Cov.: 32 AF XY: 0.653 AC XY: 48513 AN XY: 74306

African (AFR) AF: 0.870 AC: 36096 AN: 41498

American (AMR) AF: 0.571 AC: 8720 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2234 AN: 3464

East Asian (EAS) AF: 0.466 AC: 2408 AN: 5166

South Asian (SAS) AF: 0.619 AC: 2980 AN: 4816

European-Finnish (FIN) AF: 0.557 AC: 5865 AN: 10526

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39618 AN: 67988

Other (OTH) AF: 0.634 AC: 1341 AN: 2114

Alfa AF: 0.624 Hom.: 3628

Bravo AF: 0.666

Asia WGS AF: 0.593 AC: 2065 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.54
DANN	Benign	0.43
PhyloP100		-0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs7642; hg19: chr2-69547236;