NM_004962.5:c.320-4154T>C

Variant names:

• chr10-47305642-T-C
• rs12769499
• NM_004962.5:c.320-4154T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004962.5(GDF10):​c.320-4154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,156 control chromosomes in the GnomAD database, including 1,316 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 0.12 (1316 hom., cov: 32)
• Consequence: GDF10 NM_004962.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF10	NM_004962.5	c.320-4154T>C		intron_variant	Intron 1 of 2	ENST00000580279.2	NP_004953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF10	ENST00000580279.2	c.320-4154T>C		intron_variant	Intron 1 of 2	1	NM_004962.5	ENSP00000464145.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18128 AN: 152040 Hom.: 1316 Cov.: 32

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0367

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.119 AC: 18128 AN: 152156 Hom.: 1316 Cov.: 32 AF XY: 0.119 AC XY: 8883 AN XY: 74400

African (AFR) AF: 0.0420 AC: 1744 AN: 41526

American (AMR) AF: 0.0999 AC: 1529 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3466

East Asian (EAS) AF: 0.0366 AC: 189 AN: 5162

South Asian (SAS) AF: 0.150 AC: 721 AN: 4812

European-Finnish (FIN) AF: 0.166 AC: 1761 AN: 10594

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.166 AC: 11317 AN: 67986

Other (OTH) AF: 0.131 AC: 276 AN: 2108

Alfa AF: 0.116 Hom.: 374

Bravo AF: 0.109

Asia WGS AF: 0.116 AC: 403 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	2.7
DANN	Benign	0.41
PhyloP100		0.059

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: rs12769499; hg19: chr10-48433720;