19-3094925-C-T

Variant summary

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

The NM_002067.5(GNA11):c.136+138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 542,754 control chromosomes in the GnomAD database, including 1,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.077 (659 hom., cov: 30)
  • Exomes 𝑓: 0.063 (1108 hom.)
• Consequence: GNA11 NM_002067.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.28

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=-0.87).
• BP6: Variant 19-3094925-C-T is Benign according to our data. Variant chr19-3094925-C-T is described in ClinVar as [Benign]. Clinvar id is 1232179.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA11	NM_002067.5	c.136+138C>T		intron_variant		ENST00000078429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA11	ENST00000078429.9	c.136+138C>T		intron_variant		1	NM_002067.5	P1
GNA11	ENST00000586763.1	n.139+138C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11378 AN: 148820 Hom.: 648 Cov.: 30

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.0103

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0244

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0964

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0134

Gnomad NFE AF: 0.0547

Gnomad OTH AF: 0.0632

GnomAD4 exome AF: 0.0626 AC: 24649 AN: 393824 Hom.: 1108 AF XY: 0.0627 AC XY: 13088 AN XY: 208664

Gnomad4 AFR exome AF: 0.0606

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.0235

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.0864

Gnomad4 FIN exome AF: 0.0634

Gnomad4 NFE exome AF: 0.0493

Gnomad4 OTH exome AF: 0.0634

GnomAD4 genome AF: 0.0766 AC: 11404 AN: 148930 Hom.: 659 Cov.: 30 AF XY: 0.0800 AC XY: 5814 AN XY: 72646

Gnomad4 AFR AF: 0.0642

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.0244

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0965

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.0547

Gnomad4 OTH AF: 0.0625

Alfa AF: 0.0642 Hom.: 63

Bravo AF: 0.0843

Asia WGS AF: 0.132 AC: 458 AN: 3474

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

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.5
Dann	Benign	0.87

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: rs12459813; hg19: chr19-3094923;