2-69354571-G-T

Variant names:

• chr2-69354571-G-T
• NM_001244710.2:c.606-3C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001244710.2(GFPT1):​c.606-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GFPT1 NM_001244710.2 splice_region, intron
• Scores: Splicing: ADA: 0.7714
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFPT1	NM_001244710.2	c.606-3C>A		splice_region_variant, intron_variant	Intron 7 of 19	ENST00000357308.9	NP_001231639.1
GFPT1	NM_002056.4	c.606-3C>A		splice_region_variant, intron_variant	Intron 7 of 18		NP_002047.2
GFPT1	XM_017003801.2	c.681-3C>A		splice_region_variant, intron_variant	Intron 7 of 19		XP_016859290.1
GFPT1	XM_017003802.3	c.681-3C>A		splice_region_variant, intron_variant	Intron 7 of 18		XP_016859291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFPT1	ENST00000357308.9	c.606-3C>A		splice_region_variant, intron_variant	Intron 7 of 19	5	NM_001244710.2	ENSP00000349860.4
GFPT1	ENST00000361060.5	c.606-3C>A		splice_region_variant, intron_variant	Intron 7 of 18	1		ENSP00000354347.4
GFPT1	ENST00000674507.1	c.606-3C>A		splice_region_variant, intron_variant	Intron 7 of 17			ENSP00000501332.1
GFPT1	ENST00000674438.1	c.390-3C>A		splice_region_variant, intron_variant	Intron 5 of 16			ENSP00000501469.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440956 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 718318

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.77
dbscSNV1_RF	Benign	0.52
SpliceAI score (max)		0.87		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.87		Position offset: -3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-69581703;