rs10952

Variant names:

• chr5-138252651-T-A
• rs10952
• NM_001496.4:c.*317A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001496.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFRA3	NM_001496.4	MANE Select	c.*317A>T		3_prime_UTR	Exon 8 of 8	NP_001487.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFRA3	ENST00000274721.8	TSL:1 MANE Select	c.*317A>T		3_prime_UTR	Exon 8 of 8	ENSP00000274721.3
	GFRA3	ENST00000378362.3	TSL:1	c.*317A>T		3_prime_UTR	Exon 7 of 7	ENSP00000367613.3
	GFRA3	ENST00000714689.1		c.*317A>T		3_prime_UTR	Exon 8 of 8	ENSP00000519918.1

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

African (AFR) AF: 0.126 AC: 370 AN: 2944

American (AMR) AF: 0.384 AC: 1797 AN: 4678

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 703 AN: 2488

East Asian (EAS) AF: 0.309 AC: 1580 AN: 5110

South Asian (SAS) AF: 0.403 AC: 3120 AN: 7750

European-Finnish (FIN) AF: 0.290 AC: 1215 AN: 4186

Middle Eastern (MID) AF: 0.251 AC: 98 AN: 390

European-Non Finnish (NFE) AF: 0.339 AC: 17498 AN: 51546

Other (OTH) AF: 0.323 AC: 1580 AN: 4892

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

African (AFR) AF: 0.150 AC: 6213 AN: 41518

American (AMR) AF: 0.387 AC: 5895 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1111 AN: 3468

East Asian (EAS) AF: 0.294 AC: 1511 AN: 5146

South Asian (SAS) AF: 0.420 AC: 2023 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3480 AN: 10552

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24797 AN: 67922

Other (OTH) AF: 0.295 AC: 623 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.73
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10952; hg19: chr5-137588340;