Genetic Variant NM_021176.3:c.1035G>C (chr2-168908046-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021176.3(G6PC2):c.1035G>C(p.Met345Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

G6PC2
NM_021176.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.147

Publications

0 publications found

Variant links:

Genes affected

G6PC2 (HGNC:28906): (glucose-6-phosphatase catalytic subunit 2) This gene encodes an enzyme belonging to the glucose-6-phosphatase catalytic subunit family. These enzymes are part of a multicomponent integral membrane system that catalyzes the hydrolysis of glucose-6-phosphate, the terminal step in gluconeogenic and glycogenolytic pathways, allowing the release of glucose into the bloodstream. The family member encoded by this gene is found in pancreatic islets and does not exhibit phosphohydrolase activity, but it is a major target of cell-mediated autoimmunity in diabetes. Several alternatively spliced transcript variants of this gene have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

G6PC2 links:

SPC25 (HGNC:24031): (SPC25 component of NDC80 kinetochore complex) This gene encodes a protein that may be involved in kinetochore-microtubule interaction and spindle checkpoint activity. [provided by RefSeq, Jul 2008]

SPC25 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07488561).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021176.3. 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
	G6PC2	NM_021176.3	MANE Select	c.1035G>C	p.Met345Ile	missense	Exon 5 of 5	NP_066999.1	Q9NQR9-1
	G6PC2	NM_001081686.2		c.*454G>C		3_prime_UTR	Exon 4 of 4	NP_001075155.1	Q9NQR9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
G6PC2	ENST00000375363.8	TSL:1 MANE Select	c.1035G>C	p.Met345Ile	missense	Exon 5 of 5	ENSP00000364512.3	Q9NQR9-1
G6PC2	ENST00000282075.5	TSL:1	n.*616G>C		non_coding_transcript_exon	Exon 4 of 4	ENSP00000282075.4	Q9NQR9-2
G6PC2	ENST00000461586.1	TSL:1	n.635G>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

3.3

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.19

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.32

M_CAP

Benign

0.024

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.4

PhyloP100

0.15

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.81

REVEL

Benign

0.17

Sift

Benign

0.43

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.11

MutPred

0.32

Loss of MoRF binding (P = 0.0733)

MVP

0.53

MPC

0.032

ClinPred

0.096

GERP RS

4.0

Varity_R

0.084

gMVP

0.16

Mutation Taster

=94/6

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over