rs78512814

Variant names:

• chr12-48119238-G-A
• rs78512814
• NM_001354740.1:c.-89G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-48119238-G-A
• chr12-48119238-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001354740.1(PFKM):​c.-89G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000121 in 829,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: PFKM NM_001354740.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50

Genes affected

PFKM (HGNC:8877): (phosphofructokinase, muscle) Three phosphofructokinase isozymes exist in humans: muscle, liver and platelet. These isozymes function as subunits of the mammalian tetramer phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate. Tetramer composition varies depending on tissue type. This gene encodes the muscle-type isozyme. Mutations in this gene have been associated with glycogen storage disease type VII, also known as Tarui disease. Alternatively spliced transcript variants have been described.[provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFKM	NM_001354740.1	c.-89G>A		5_prime_UTR_variant	Exon 1 of 23		NP_001341669.1
PFKM	XM_047429003.1	c.-89G>A		5_prime_UTR_variant	Exon 1 of 22		XP_047284959.1
PFKM	NM_001354735.1	c.301+661G>A		intron_variant	Intron 4 of 25		NP_001341664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKM	ENST00000642730.1	c.301+661G>A		intron_variant	Intron 4 of 25			ENSP00000496597.1
PFKM	ENST00000550257.7	c.215-3529G>A		intron_variant	Intron 2 of 23	4		ENSP00000447997.3
PFKM	ENST00000340802.12	c.206-3529G>A		intron_variant	Intron 3 of 24	2		ENSP00000345771.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000121 AC: 1 AN: 829652 Hom.: 0 Cov.: 19 AF XY: 0.00000261 AC XY: 1 AN XY: 383322

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: 0.00000132

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs78512814; hg19: chr12-48513021;