rs10036665

chr5-138252460-T-Achr5-138252460-T-C

Variant summary

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

The NM_001496.4(GFRA3):c.*508A>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 0.159 in 154,162 control chromosomes in the GnomAD database, including 2,105 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 0.16 (2082 hom., cov: 32)
  • Exomes 𝑓: 0.15 (23 hom.)
• Consequence: GFRA3 NM_001496.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFRA3	NM_001496.4	c.*508A>T		3_prime_UTR_variant	8/8	ENST00000274721.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFRA3	ENST00000274721.8	c.*508A>T		3_prime_UTR_variant	8/8	1	NM_001496.4	P2
GFRA3	ENST00000378362.3	c.*508A>T		3_prime_UTR_variant	7/7	1		A2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24187 AN: 152066 Hom.: 2085 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.152 AC: 301 AN: 1978 Hom.: 23 Cov.: 0 AF XY: 0.146 AC XY: 161 AN XY: 1106

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0556

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.159 AC: 24194 AN: 152184 Hom.: 2082 Cov.: 32 AF XY: 0.158 AC XY: 11772 AN XY: 74388

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.188

Alfa AF: 0.100 Hom.: 145

Bravo AF: 0.156

Asia WGS AF: 0.115 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	4.0
Dann	Benign	0.41

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: rs10036665; hg19: chr5-137588149;