NM_006572.6:c.511-4112T>C

Variant names:

• chr17-65022415-A-G
• rs3972219
• NM_006572.6:c.511-4112T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006572.6(GNA13):​c.511-4112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 151,676 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.042 (199 hom., cov: 31)
• Consequence: GNA13 NM_006572.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 3 publications found

Genes affected

GNA13 (HGNC:4381): (G protein subunit alpha 13) Predicted to enable D5 dopamine receptor binding activity; G-protein beta/gamma-subunit complex binding activity; and GTPase activity. Predicted to be involved in several processes, including Rho protein signal transduction; activation of phospholipase D activity; and multicellular organism aging. Predicted to act upstream of or within several processes, including branching involved in blood vessel morphogenesis; negative regulation of vascular associated smooth muscle cell migration; and negative regulation of vascular associated smooth muscle cell proliferation. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006572.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA13	NM_006572.6	MANE Select	c.511-4112T>C		intron	N/A	NP_006563.2
	GNA13	NM_001282425.2		c.226-4112T>C		intron	N/A	NP_001269354.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA13	ENST00000439174.7	TSL:1 MANE Select	c.511-4112T>C		intron	N/A	ENSP00000400717.2
	GNA13	ENST00000541118.1	TSL:2	c.226-4112T>C		intron	N/A	ENSP00000439647.1

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6424 AN: 151562 Hom.: 199 Cov.: 31

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.0664

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.0350

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0424 AC: 6427 AN: 151676 Hom.: 199 Cov.: 31 AF XY: 0.0422 AC XY: 3128 AN XY: 74120

African (AFR) AF: 0.0112 AC: 462 AN: 41422

American (AMR) AF: 0.0277 AC: 422 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0664 AC: 230 AN: 3464

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5172

South Asian (SAS) AF: 0.0254 AC: 122 AN: 4808

European-Finnish (FIN) AF: 0.0733 AC: 764 AN: 10416

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0635 AC: 4309 AN: 67832

Other (OTH) AF: 0.0346 AC: 73 AN: 2110

Alfa AF: 0.0565 Hom.: 256

Bravo AF: 0.0386

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.20
DANN	Benign	0.37
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs3972219; hg19: chr17-63018533;