Variant chr7-2795139-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007353.3(GNA12):c.314C>T(p.Ser105Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000617 in 1,458,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GNA12
NM_007353.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.44

Variant links:

Genes affected

GNA12 (HGNC:4380): (G protein subunit alpha 12) Predicted to enable D5 dopamine receptor binding activity; G-protein beta/gamma-subunit complex binding activity; and GTPase activity. Involved in regulation of TOR signaling and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

GNA12 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23876053).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GNA12	NM_007353.3 linkuse as main transcript	c.314C>T	p.Ser105Leu	missense_variant	2/4	ENST00000275364.8
GNA12	NM_001293092.2 linkuse as main transcript	c.314C>T	p.Ser105Leu	missense_variant	2/3
GNA12	NM_001282441.2 linkuse as main transcript	c.137C>T	p.Ser46Leu	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA12	ENST00000275364.8 linkuse as main transcript	c.314C>T	p.Ser105Leu	missense_variant	2/4	1	NM_007353.3	P1	Q03113-1
GNA12	ENST00000407904.7 linkuse as main transcript	c.137C>T	p.Ser46Leu	missense_variant	3/5	2			Q03113-2
GNA12	ENST00000447791.1 linkuse as main transcript	c.59C>T	p.Ser20Leu	missense_variant	2/2	4
GNA12	ENST00000471281.5 linkuse as main transcript	n.7C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000617

AC:

AN:

1458050

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725706

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:

0.00000812

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 05, 2024

The c.314C>T (p.S105L) alteration is located in exon 2 (coding exon 2) of the GNA12 gene. This alteration results from a C to T substitution at nucleotide position 314, causing the serine (S) at amino acid position 105 to be replaced by a leucine (L). 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

0.16

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Benign

0.85

DEOGEN2

Benign

0.26

T;.;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

-1.1

N;.;.

MutationTaster

Benign

0.76

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

2.1

N;N;N

REVEL

Uncertain

0.45

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.052

B;.;.

Vest4

0.57

MutPred

0.54

Gain of helix (P = 0.0082);.;.;

MVP

0.81

MPC

0.57

ClinPred

0.48

GERP RS

5.6

Varity_R

0.070

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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