chr19-3151717-C-T

Variant names:

• chr19-3151717-C-T
• rs1914885378
• NM_002068.4:c.496C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002068.4(GNA15):​c.496C>T​(p.His166Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNA15 NM_002068.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.730
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3495584).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002068.4. 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
	GNA15	NM_002068.4	MANE Select	c.496C>T	p.His166Tyr	missense	Exon 4 of 7	NP_002059.3	P30679
	GNA15-DT	NR_110670.1		n.159-1927G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA15	ENST00000262958.4	TSL:1 MANE Select	c.496C>T	p.His166Tyr	missense	Exon 4 of 7	ENSP00000262958.2	P30679
	GNA15	ENST00000586082.1	TSL:3	n.457C>T		non_coding_transcript_exon	Exon 2 of 3
	GNA15	ENST00000592455.1	TSL:3	n.*526C>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000467256.1	K7EP74

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.98
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.28	N
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	0.064	D
PhyloP100		0.73
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.025	D
Vest4		0.37
MutPred		0.65		Loss of disorder (P = 0.0857)
MVP		0.89
MPC		0.95
ClinPred		0.80	D
GERP RS		0.85
gMVP		0.65
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1914885378; hg19: chr19-3151715;