rs3007

chr10-47313015-A-T

Variant summary

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

The NM_004962.5(GDF10):c.*223A>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 0.21 in 406,996 control chromosomes in the GnomAD database, including 9,443 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 0.22 (3648 hom., cov: 33)
  • Exomes 𝑓: 0.21 (5795 hom.)
• Consequence: GDF10 NM_004962.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.990

Genes affected

GDF10 (HGNC:4215): (growth differentiation factor 10) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This promotes neural repair after stroke. Additionally, this protein may act as a tumor suppressor and reduced expression of this gene is associated with oral cancer. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF10	NM_004962.5	c.*223A>T		3_prime_UTR_variant	3/3	ENST00000580279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF10	ENST00000580279.2	c.*223A>T		3_prime_UTR_variant	3/3	1	NM_004962.5	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32746 AN: 152040 Hom.: 3645 Cov.: 33

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.207 AC: 52733 AN: 254838 Hom.: 5795 Cov.: 0 AF XY: 0.207 AC XY: 26903 AN XY: 129868

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.215 AC: 32768 AN: 152158 Hom.: 3648 Cov.: 33 AF XY: 0.216 AC XY: 16083 AN XY: 74394

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.202

Alfa AF: 0.201 Hom.: 421

Bravo AF: 0.213

Asia WGS AF: 0.261 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	12
Dann	Benign	0.88

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: rs3007; hg19: chr10-48426347;