NM_000294.3:c.*194C>T

Variant names:

• chr16-30757291-C-T
• rs1061190
• NM_000294.3:c.*194C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000294.3(PHKG2):​c.*194C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,387,746 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PHKG2 NM_000294.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 1 publications found

Genes affected

PHKG2 (HGNC:8931): (phosphorylase kinase catalytic subunit gamma 2) Phosphorylase kinase is a polymer of 16 subunits, four each of alpha, beta, gamma and delta. The alpha subunit includes the skeletal muscle and hepatic isoforms, encoded by two different genes. The beta subunit is the same in both the muscle and hepatic isoforms, and encoded by one gene. The gamma subunit also includes the skeletal muscle and hepatic isoforms, and the hepatic isoform is encoded by this gene. The delta subunit is a calmodulin and can be encoded by three different genes. The gamma subunits contain the active site of the enzyme, whereas the alpha and beta subunits have regulatory functions controlled by phosphorylation. The delta subunit mediates the dependence of the enzyme on calcium concentration. Mutations in this gene cause glycogen storage disease type 9C, also known as autosomal liver glycogenosis. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

CFAP119 (HGNC:28078): (cilia and flagella associated protein 119)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000294.3. 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
	PHKG2	NM_000294.3	MANE Select	c.*194C>T		3_prime_UTR	Exon 10 of 10	NP_000285.1	P15735-1
	PHKG2	NM_001172432.2		c.1083+332C>T		intron	N/A	NP_001165903.1	P15735-2
	CFAP119	NM_001014979.3	MANE Select	c.*185G>A		downstream_gene	N/A	NP_001014979.2	A1A4V9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHKG2	ENST00000563588.6	TSL:1 MANE Select	c.*194C>T		3_prime_UTR	Exon 10 of 10	ENSP00000455607.1	P15735-1
	PHKG2	ENST00000328273.11	TSL:5	c.*194C>T		3_prime_UTR	Exon 10 of 10	ENSP00000329968.7	J3KNN3
	PHKG2	ENST00000915464.1		c.*194C>T		3_prime_UTR	Exon 9 of 9	ENSP00000585523.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1387746 Hom.: 0 Cov.: 34 AF XY: 0.00000292 AC XY: 2 AN XY: 684938

African (AFR) AF: 0.00 AC: 0 AN: 31432

American (AMR) AF: 0.00 AC: 0 AN: 36172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21838

East Asian (EAS) AF: 0.00 AC: 0 AN: 39174

South Asian (SAS) AF: 0.0000132 AC: 1 AN: 75516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4102

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1083822

Other (OTH) AF: 0.00 AC: 0 AN: 57456

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.0
DANN	Benign	0.83
PhyloP100		-0.49

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: rs1061190; hg19: chr16-30768612;