Variant 19-3094680-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3

The NM_002067.5(GNA11):c.29G>A(p.Cys10Tyr) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GNA11
NM_002067.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

Variant links:

Genes affected

GNA11 (HGNC:4379): (G protein subunit alpha 11) The protein encoded by this gene belongs to the family of guanine nucleotide-binding proteins (G proteins), which function as modulators or transducers in various transmembrane signaling systems. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes one of the alpha subunits (subunit alpha-11). Mutations in this gene have been associated with hypocalciuric hypercalcemia type II (HHC2) and hypocalcemia dominant 2 (HYPOC2). Patients with HHC2 and HYPOC2 exhibit decreased or increased sensitivity, respectively, to changes in extracellular calcium concentrations. [provided by RefSeq, Dec 2013]

GNA11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a lipid_moiety_binding_region S-palmitoyl cysteine (size 0) in uniprot entity GNA11_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), GNA11. . Gene score misZ: 3.768 (greater than the threshold 3.09). Trascript score misZ: 3.8723 (greater than threshold 3.09). The gene has 13 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. GenCC has associacion of the gene with autosomal dominant hypocalcemia, familial hypocalciuric hypercalcemia 2, autosomal dominant hypocalcemia 2.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNA11	NM_002067.5 link	c.29G>A	p.Cys10Tyr	missense_variant	1/7	ENST00000078429.9	NP_002058.2	P29992

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNA11	ENST00000078429.9 link	c.29G>A	p.Cys10Tyr	missense_variant	1/7	1	NM_002067.5	ENSP00000078429.3		P29992
GNA11	ENST00000586763.1 link	n.32G>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1416596

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704452

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial hypocalciuric hypercalcemia 2;C3809243:Autosomal dominant hypocalcemia 2

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jun 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.82

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.79

MetaRNN

Pathogenic

0.80

MetaSVM

Uncertain

0.63

MutationAssessor

Pathogenic

3.3

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-6.7

REVEL

Pathogenic

0.77

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.036

Polyphen

1.0

Vest4

0.49

MutPred

0.49

Loss of catalytic residue at L11 (P = 0.011);

MVP

0.85

MPC

2.8

ClinPred

0.99

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.77

gMVP

0.90

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over