19-3094529-G-A

Position:

• chr19-3094529-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000078429.9(GNA11):​c.-123G>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 0.026 in 206,714 control chromosomes in the GnomAD database, including 201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (193 hom., cov: 30)
  • Exomes 𝑓: 0.0086 (8 hom.)
• Consequence: GNA11 ENST00000078429.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.289

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-3094529-G-A is Benign according to our data. Variant chr19-3094529-G-A is described in ClinVar as [Benign]. Clinvar id is 1229520.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNA11	NM_002067.5	c.-123G>A		5_prime_UTR_variant	1/7	ENST00000078429.9	NP_002058.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNA11	ENST00000078429.9	c.-123G>A		5_prime_UTR_variant	1/7	1	NM_002067.5	ENSP00000078429	P1

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 4835 AN: 144348 Hom.: 193 Cov.: 30

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00491

Gnomad SAS AF: 0.00169

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.0103

Gnomad NFE AF: 0.00690

Gnomad OTH AF: 0.0286

GnomAD4 exome AF: 0.00862 AC: 538 AN: 62388 Hom.: 8 Cov.: 3 AF XY: 0.00873 AC XY: 263 AN XY: 30138

Gnomad4 AFR exome AF: 0.0730

Gnomad4 AMR exome AF: 0.0256

Gnomad4 ASJ exome AF: 0.0114

Gnomad4 EAS exome AF: 0.00459

Gnomad4 SAS exome AF: 0.00154

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00679

Gnomad4 OTH exome AF: 0.0134

GnomAD4 genome AF: 0.0335 AC: 4835 AN: 144326 Hom.: 193 Cov.: 30 AF XY: 0.0327 AC XY: 2291 AN XY: 70070

Gnomad4 AFR AF: 0.0935

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.00493

Gnomad4 SAS AF: 0.00170

Gnomad4 FIN AF: 0.0125

Gnomad4 NFE AF: 0.00691

Gnomad4 OTH AF: 0.0284

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.95

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

LitVar

Other links and lift over

dbSNP: rs866779785; hg19: chr19-3094527;