rs10952

Positions:

• chr5-138252651-T-A
• chr5-138252651-T-G

Variant summary

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

The NM_001496.4(GFRA3):​c.*317A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 235,960 control chromosomes in the GnomAD database, including 12,878 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 0.30 (7799 hom., cov: 31)
  • Exomes 𝑓: 0.33 (5079 hom.)
• Consequence: GFRA3 NM_001496.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491

Genes affected

GFRA3 (HGNC:4245): (GDNF family receptor alpha 3) The protein encoded by this gene is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor and a member of the GDNF receptor family. It forms a signaling receptor complex with RET tyrosine kinase receptor and binds the ligand, artemin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFRA3	NM_001496.4	c.*317A>T		3_prime_UTR_variant	8/8	ENST00000274721.8	NP_001487.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFRA3	ENST00000274721.8	c.*317A>T		3_prime_UTR_variant	8/8	1	NM_001496.4	ENSP00000274721	P2
GFRA3	ENST00000378362.3	c.*317A>T		3_prime_UTR_variant	7/7	1		ENSP00000367613	A2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45856 AN: 151858 Hom.: 7790 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.333 AC: 27961 AN: 83984 Hom.: 5079 Cov.: 0 AF XY: 0.339 AC XY: 14654 AN XY: 43244

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.302 AC: 45888 AN: 151976 Hom.: 7799 Cov.: 31 AF XY: 0.304 AC XY: 22583 AN XY: 74248

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.295

Alfa AF: 0.310 Hom.: 1057

Bravo AF: 0.297

Asia WGS AF: 0.330 AC: 1148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10952; hg19: chr5-137588340;