chr7-2814361-C-T

Variant names:

• chr7-2814361-C-T
• rs151253462
• NM_007353.3:c.310-19218G>A

Variant summary

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

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.109

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]

ACMG classification

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
GNA12	NM_007353.3	c.310-19218G>A		intron_variant	Intron 1 of 3	ENST00000275364.8	NP_031379.2
GNA12	NM_001282441.2	c.83G>A	p.Arg28Gln	missense_variant	Exon 2 of 5		NP_001269370.1
GNA12	NM_001293092.2	c.310-19218G>A		intron_variant	Intron 1 of 2		NP_001280021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNA12	ENST00000275364.8	c.310-19218G>A		intron_variant	Intron 1 of 3	1	NM_007353.3	ENSP00000275364.3
GNA12	ENST00000407904.7	c.83G>A	p.Arg28Gln	missense_variant	Exon 2 of 5	2		ENSP00000385935.3
GNA12	ENST00000447791.1	c.54+516G>A		intron_variant	Intron 1 of 1	4		ENSP00000391462.1

Frequencies

GnomAD3 genomes AF: 0.00594 AC: 902 AN: 151892 Hom.: 6 Cov.: 31

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

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

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

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

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

Other links and lift over

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