Variant 9-77431409-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_004297.4(GNA14):c.505G>A(p.Val169Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

GNA14
NM_004297.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.326

Variant links:

Genes affected

GNA14 (HGNC:4382): (G protein subunit alpha 14) This gene encodes a member of the guanine nucleotide-binding, or G protein family. G proteins are heterotrimers consisting of alpha, beta and gamma subunits. The encoded protein is a member of the alpha family of G proteins, more specifically the alpha q subfamily of G proteins. The encoded protein may play a role in pertussis-toxin resistant activation of phospholipase C-beta and its downstream effectors.[provided by RefSeq, Feb 2009]

GNA14 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4004826).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA14	NM_004297.4 linkuse as main transcript	c.505G>A	p.Val169Met	missense_variant	4/7	ENST00000341700.7
GNA14	XM_047424110.1 linkuse as main transcript	c.151G>A	p.Val51Met	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA14	ENST00000341700.7 linkuse as main transcript	c.505G>A	p.Val169Met	missense_variant	4/7	1	NM_004297.4	P1
GNA14	ENST00000464095.1 linkuse as main transcript	n.280G>A		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461296

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726980

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000108

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.505G>A (p.V169M) alteration is located in exon 4 (coding exon 4) of the GNA14 gene. This alteration results from a G to A substitution at nucleotide position 505, causing the valine (V) at amino acid position 169 to be replaced by a methionine (M). 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

0.14

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.31

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.065

MetaRNN

Benign

0.40

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

0.89

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.31

REVEL

Uncertain

0.30

Sift

Benign

0.11

Sift4G

Benign

0.17

Polyphen

0.020

Vest4

0.49

MutPred

0.48

Loss of phosphorylation at T171 (P = 0.0987);

MVP

0.89

MPC

0.13

ClinPred

0.20

GERP RS

5.4

Varity_R

0.021

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over