19-3151825-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002068.4(GNA15):c.604A>G(p.Thr202Ala) 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. 11/19 in silico tools predict 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: 0.758

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1932719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA15	NM_002068.4	c.604A>G	p.Thr202Ala	missense_variant	4/7	ENST00000262958.4
GNA15-DT	NR_110670.1	n.159-2035T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA15	ENST00000262958.4	c.604A>G	p.Thr202Ala	missense_variant	4/7	1	NM_002068.4	P1
GNA15-DT	ENST00000587587.1	n.159-2035T>C		intron_variant, non_coding_transcript_variant		2
GNA15	ENST00000586082.1	n.565A>G		non_coding_transcript_exon_variant	2/3	3
GNA15	ENST00000592455.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2023

The c.604A>G (p.T202A) alteration is located in exon 4 (coding exon 4) of the GNA15 gene. This alteration results from a A to G substitution at nucleotide position 604, causing the threonine (T) at amino acid position 202 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	21
Dann	Uncertain	0.99
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.60	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.60	T
MutationTaster	Benign	0.94	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.57	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.010	D
Sift4G	Benign	0.071	T
Vest4		0.39
MutPred		0.47		Gain of sheet (P = 0.0827);
MVP		0.80
MPC		0.85
ClinPred		0.25	T
GERP RS		4.5
gMVP		0.55

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.

Other links and lift over

hg19: chr19-3151823;