9-127345685-A-G

Position:

• chr9-127345685-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032293.5(GARNL3):​c.1431+208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 152,122 control chromosomes in the GnomAD database, including 27,670 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 0.60 (27670 hom., cov: 33)
• Consequence: GARNL3 NM_032293.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.941

Genes affected

GARNL3 (HGNC:25425): (GTPase activating Rap/RanGAP domain like 3) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GARNL3	NM_032293.5	c.1431+208A>G		intron_variant		ENST00000373387.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GARNL3	ENST00000373387.9	c.1431+208A>G		intron_variant		1	NM_032293.5	A2
GARNL3	ENST00000435213.6	c.1365+208A>G		intron_variant		2		P4
GARNL3	ENST00000373386.6	c.1377+208A>G		intron_variant, NMD_transcript_variant		2
GARNL3	ENST00000460176.6	c.200+208A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.599 AC: 91081 AN: 152002 Hom.: 27642 Cov.: 33

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.599 AC: 91153 AN: 152122 Hom.: 27670 Cov.: 33 AF XY: 0.598 AC XY: 44497 AN XY: 74356

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.593

Alfa AF: 0.562 Hom.: 55260

Bravo AF: 0.610

Asia WGS AF: 0.532 AC: 1849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.010
DANN	Benign	0.49

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: rs4130590; hg19: chr9-130107964;