chr7-2814361-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001282441.2(GNA12):​c.83G>A​(p.Arg28Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00774 in 1,603,128 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 31)
Exomes 𝑓: 0.0079 ( 70 hom. )

Consequence

GNA12
NM_001282441.2 missense

Scores

3
11

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.109
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004283428).
BP6
Variant 7-2814361-C-T is Benign according to our data. Variant chr7-2814361-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657237.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00793 (11507/1451118) while in subpopulation MID AF= 0.0254 (146/5744). AF 95% confidence interval is 0.0221. There are 70 homozygotes in gnomad4_exome. There are 5671 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.
BS2
High AC in GnomAd4 at 904 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GNA12NM_007353.3 linkc.310-19218G>A intron_variant Intron 1 of 3 ENST00000275364.8 NP_031379.2 Q03113-1Q6ZQV4
GNA12NM_001282441.2 linkc.83G>A p.Arg28Gln missense_variant Exon 2 of 5 NP_001269370.1 Q03113-2
GNA12NM_001293092.2 linkc.310-19218G>A intron_variant Intron 1 of 2 NP_001280021.1 Q03113

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GNA12ENST00000275364.8 linkc.310-19218G>A intron_variant Intron 1 of 3 1 NM_007353.3 ENSP00000275364.3 Q03113-1
GNA12ENST00000407904.7 linkc.83G>A p.Arg28Gln missense_variant Exon 2 of 5 2 ENSP00000385935.3 Q03113-2
GNA12ENST00000447791.1 linkc.54+516G>A intron_variant Intron 1 of 1 4 ENSP00000391462.1 C9J2Y7

Frequencies

GnomAD3 genomes
AF:
0.00594
AC:
902
AN:
151892
Hom.:
6
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00157
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00617
Gnomad ASJ
AF:
0.00922
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00374
Gnomad FIN
AF:
0.00104
Gnomad MID
AF:
0.0380
Gnomad NFE
AF:
0.00956
Gnomad OTH
AF:
0.00909
GnomAD3 exomes
AF:
0.00607
AC:
1467
AN:
241542
Hom.:
11
AF XY:
0.00655
AC XY:
869
AN XY:
132636
show subpopulations
Gnomad AFR exome
AF:
0.00133
Gnomad AMR exome
AF:
0.00366
Gnomad ASJ exome
AF:
0.0108
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00273
Gnomad FIN exome
AF:
0.000975
Gnomad NFE exome
AF:
0.00998
Gnomad OTH exome
AF:
0.00686
GnomAD4 exome
AF:
0.00793
AC:
11507
AN:
1451118
Hom.:
70
Cov.:
27
AF XY:
0.00785
AC XY:
5671
AN XY:
722500
show subpopulations
Gnomad4 AFR exome
AF:
0.00192
Gnomad4 AMR exome
AF:
0.00423
Gnomad4 ASJ exome
AF:
0.0103
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00305
Gnomad4 FIN exome
AF:
0.000937
Gnomad4 NFE exome
AF:
0.00909
Gnomad4 OTH exome
AF:
0.00831
GnomAD4 genome
AF:
0.00595
AC:
904
AN:
152010
Hom.:
6
Cov.:
31
AF XY:
0.00583
AC XY:
433
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.00159
Gnomad4 AMR
AF:
0.00616
Gnomad4 ASJ
AF:
0.00922
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00375
Gnomad4 FIN
AF:
0.00104
Gnomad4 NFE
AF:
0.00956
Gnomad4 OTH
AF:
0.00900
Alfa
AF:
0.00806
Hom.:
2
Bravo
AF:
0.00640
TwinsUK
AF:
0.00836
AC:
31
ALSPAC
AF:
0.00986
AC:
38
ESP6500AA
AF:
0.00171
AC:
3
ESP6500EA
AF:
0.00779
AC:
31
ExAC
AF:
0.00639
AC:
741
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.0114
EpiControl
AF:
0.0120

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Dec 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

GNA12: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
10
DANN
Uncertain
0.99
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.35
T
MetaRNN
Benign
0.0043
T
MetaSVM
Benign
-0.52
T
PROVEAN
Benign
1.2
N
REVEL
Benign
0.17
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.014
D
Vest4
0.12
MVP
0.47
ClinPred
0.0030
T
GERP RS
2.1

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.

Other links and lift over

dbSNP: rs151253462; hg19: chr7-2853995; COSMIC: COSV51740446; API