rs199847220

Variant names:

• chr19-3151726-C-A
• rs199847220
• NM_002068.4:c.505C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3151726-C-A
• chr19-3151726-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002068.4(GNA15):​c.505C>A​(p.Arg169Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GNA15 NM_002068.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405

Genes affected

GNA15 (HGNC:4383): (G protein subunit alpha 15) Enables G protein-coupled receptor binding activity. Involved in positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway. Predicted to be located in plasma membrane. Predicted to be part of heterotrimeric G-protein complex. [provided by Alliance of Genome Resources, Apr 2022]

GNA15-DT (HGNC:55293): (GNA15 divergent transcript)

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.988

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNA15	NM_002068.4	c.505C>A	p.Arg169Ser	missense_variant	Exon 4 of 7	ENST00000262958.4	NP_002059.3
GNA15-DT	NR_110670.1	n.159-1936G>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNA15	ENST00000262958.4	c.505C>A	p.Arg169Ser	missense_variant	Exon 4 of 7	1	NM_002068.4	ENSP00000262958.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000413 AC: 1 AN: 241976 Hom.: 0 AF XY: 0.00000762 AC XY: 1 AN XY: 131254

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1451886 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 722344

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000695

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.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Pathogenic	0.42	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	0.99	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Pathogenic	0.90
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.97
MutPred		0.89		Gain of disorder (P = 0.0486);
MVP		0.98
MPC		1.6
ClinPred		0.93	D
GERP RS		4.6
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

LitVar

Other links and lift over

dbSNP: rs199847220; hg19: chr19-3151724;