rs879750913

Variant names:

• chr2-69320787-CAAAA-C
• rs879750913
• NM_001244710.2:c.*5398_*5401delTTTT

Your query was ambiguous. Multiple possible variants found:

• chr2-69320787-CAAAA-C
• chr2-69320787-CAAAA-CA
• chr2-69320787-CAAAA-CAA
• chr2-69320787-CAAAA-CAAA
• chr2-69320787-CAAAA-CAAAAA
• chr2-69320787-CAAAA-CAAAAAA
• chr2-69320787-CAAAA-CAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001244710.2(GFPT1):​c.*5398_*5401delTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000812 in 123,166 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000081 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GFPT1 NM_001244710.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.*5398_*5401delTTTT		3_prime_UTR	Exon 20 of 20	NP_001231639.1	Q06210-1
	GFPT1	NM_002056.4		c.*5398_*5401delTTTT		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.*5398_*5401delTTTT		3_prime_UTR	Exon 20 of 20	ENSP00000349860.4	Q06210-1
	GFPT1	ENST00000361060.5	TSL:1	c.*5398_*5401delTTTT		3_prime_UTR	Exon 19 of 19	ENSP00000354347.4	Q06210-2

Frequencies

GnomAD3 genomes AF: 0.00000812 AC: 1 AN: 123166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000159

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 84 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 66

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

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: 0.00 AC: 0 AN: 72

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00000812 AC: 1 AN: 123166 Hom.: 0 Cov.: 32 AF XY: 0.0000171 AC XY: 1 AN XY: 58508

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.00 AC: 0 AN: 11664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3078

East Asian (EAS) AF: 0.00 AC: 0 AN: 4210

South Asian (SAS) AF: 0.00 AC: 0 AN: 3744

European-Finnish (FIN) AF: 0.000159 AC: 1 AN: 6296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58166

Other (OTH) AF: 0.00 AC: 0 AN: 1646

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

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: rs879750913; hg19: chr2-69547919;