10-47308495-C-T

Variant summary

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

The NM_004962.5(GDF10):c.320-1301C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,106 control chromosomes in the GnomAD database, including 1,002 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 0.10 (1002 hom., cov: 32)
• Consequence: GDF10 NM_004962.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF10	NM_004962.5	c.320-1301C>T		intron_variant		ENST00000580279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF10	ENST00000580279.2	c.320-1301C>T		intron_variant		1	NM_004962.5	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15738 AN: 151988 Hom.: 1000 Cov.: 32

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00812

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.113

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 15748 AN: 152106 Hom.: 1002 Cov.: 32 AF XY: 0.104 AC XY: 7768 AN XY: 74350

Gnomad4 AFR AF: 0.0392

Gnomad4 AMR AF: 0.0866

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.00814

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.116

Alfa AF: 0.119 Hom.: 677

Bravo AF: 0.0945

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.8
Dann	Benign	0.68

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: rs11598444; hg19: chr10-48430867;