rs10036665

Variant names:

• chr5-138252460-T-A
• rs10036665
• NM_001496.4:c.*508A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-138252460-T-A
• chr5-138252460-T-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFRA3	NM_001496.4	MANE Select	c.*508A>T		3_prime_UTR	Exon 8 of 8	NP_001487.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFRA3	ENST00000274721.8	TSL:1 MANE Select	c.*508A>T		3_prime_UTR	Exon 8 of 8	ENSP00000274721.3
	GFRA3	ENST00000378362.3	TSL:1	c.*508A>T		3_prime_UTR	Exon 7 of 7	ENSP00000367613.3
	GFRA3	ENST00000714690.1		n.*1459A>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000519919.1

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

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AF: 0.124 AC: 31 AN: 250

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.0556 AC: 1 AN: 18

South Asian (SAS) AF: 0.114 AC: 8 AN: 70

European-Finnish (FIN) AF: 0.200 AC: 87 AN: 436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.146 AC: 166 AN: 1136

Other (OTH) AF: 0.120 AC: 6 AN: 50

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

African (AFR) AF: 0.115 AC: 4771 AN: 41514

American (AMR) AF: 0.168 AC: 2576 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3468

East Asian (EAS) AF: 0.105 AC: 541 AN: 5176

South Asian (SAS) AF: 0.111 AC: 536 AN: 4826

European-Finnish (FIN) AF: 0.194 AC: 2052 AN: 10580

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12310 AN: 68002

Other (OTH) AF: 0.188 AC: 397 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.0
DANN	Benign	0.41
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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: rs10036665; hg19: chr5-137588149;