19-3150141-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002068.4(GNA15):c.341G>A(p.Ser114Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,613,168 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (19 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (20 hom.)
• Consequence: GNA15 NM_002068.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.248

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031994283).
• BP6: Variant 19-3150141-G-A is Benign according to our data. Variant chr19-3150141-G-A is described in ClinVar as [Benign]. Clinvar id is 786961.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00918 (1398/152346) while in subpopulation AFR AF= 0.032 (1329/41572). AF 95% confidence interval is 0.0305. There are 19 homozygotes in gnomad4. There are 680 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1394 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA15	NM_002068.4	c.341G>A	p.Ser114Asn	missense_variant	3/7	ENST00000262958.4
GNA15-DT	NR_110670.1	n.159-351C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA15	ENST00000262958.4	c.341G>A	p.Ser114Asn	missense_variant	3/7	1	NM_002068.4	P1
GNA15-DT	ENST00000587587.1	n.159-351C>T		intron_variant, non_coding_transcript_variant		2
GNA15	ENST00000586082.1	n.302G>A		non_coding_transcript_exon_variant	1/3	3
GNA15	ENST00000592455.1	c.*371G>A		3_prime_UTR_variant, NMD_transcript_variant	4/5	3

Frequencies

GnomAD3 genomes AF: 0.00916 AC: 1394 AN: 152228 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00234 AC: 585 AN: 249830 Hom.: 9 AF XY: 0.00164 AC XY: 222 AN XY: 135430

Gnomad AFR exome AF: 0.0314

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000231

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00104 AC: 1520 AN: 1460822 Hom.: 20 Cov.: 31 AF XY: 0.000929 AC XY: 675 AN XY: 726714

Gnomad4 AFR exome AF: 0.0348

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000791

Gnomad4 OTH exome AF: 0.00257

GnomAD4 genome AF: 0.00918 AC: 1398 AN: 152346 Hom.: 19 Cov.: 33 AF XY: 0.00913 AC XY: 680 AN XY: 74498

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.00287

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00250 Hom.: 3

Bravo AF: 0.00991

ESP6500AA AF: 0.0306 AC: 135

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00296 AC: 359

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000297

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

Invitae

Dec 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	12
Dann	Benign	0.95
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.055	N
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.19
Sift	Benign	0.32	T
Sift4G	Benign	0.40	T
Vest4		0.063
MVP		0.64
MPC		0.53
ClinPred		0.00060	T
GERP RS		0.0092
gMVP		0.33

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: rs139115108; hg19: chr19-3150139;