10-47310388-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004962.5(GDF10):c.912G>A(p.Pro304=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,608,516 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (158 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (163 hom.)
• Consequence: GDF10 NM_004962.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.83

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-47310388-G-A is Benign according to our data. Variant chr10-47310388-G-A is described in ClinVar as [Benign]. Clinvar id is 768363.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF10	NM_004962.5	c.912G>A	p.Pro304=	synonymous_variant	2/3	ENST00000580279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF10	ENST00000580279.2	c.912G>A	p.Pro304=	synonymous_variant	2/3	1	NM_004962.5	P1

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3656 AN: 152150 Hom.: 157 Cov.: 33

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00645 AC: 1496 AN: 231916 Hom.: 60 AF XY: 0.00489 AC XY: 624 AN XY: 127484

Gnomad AFR exome AF: 0.0900

Gnomad AMR exome AF: 0.00517

Gnomad ASJ exome AF: 0.00146

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000428

Gnomad OTH exome AF: 0.00526

GnomAD4 exome AF: 0.00270 AC: 3939 AN: 1456248 Hom.: 163 Cov.: 33 AF XY: 0.00236 AC XY: 1712 AN XY: 724292

Gnomad4 AFR exome AF: 0.0875

Gnomad4 AMR exome AF: 0.00602

Gnomad4 ASJ exome AF: 0.00181

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000245

Gnomad4 OTH exome AF: 0.00657

GnomAD4 genome AF: 0.0241 AC: 3669 AN: 152268 Hom.: 158 Cov.: 33 AF XY: 0.0231 AC XY: 1719 AN XY: 74454

Gnomad4 AFR AF: 0.0832

Gnomad4 AMR AF: 0.00915

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00181 Hom.: 4

Bravo AF: 0.0286

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.14
Dann	Benign	0.92

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: rs61731868; hg19: chr10-48428974;