NM_004962.5:c.178C>T

Variant names:

• chr10-47300829-C-T
• rs782350512
• NM_004962.5:c.178C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004962.5(GDF10):​c.178C>T​(p.Pro60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000302 in 1,421,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: GDF10 NM_004962.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.187
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11024237).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004962.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF10	NM_004962.5	MANE Select	c.178C>T	p.Pro60Ser	missense	Exon 1 of 3	NP_004953.1	P55107

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF10	ENST00000580279.2	TSL:1 MANE Select	c.178C>T	p.Pro60Ser	missense	Exon 1 of 3	ENSP00000464145.1	P55107
	GDF10	ENST00000895678.1		c.178C>T	p.Pro60Ser	missense	Exon 1 of 3	ENSP00000565737.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.000195 AC: 36 AN: 184170 AF XY: 0.000137

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000302 AC: 43 AN: 1421572 Hom.: 0 Cov.: 34 AF XY: 0.0000326 AC XY: 23 AN XY: 705642

African (AFR) AF: 0.00 AC: 0 AN: 32176

American (AMR) AF: 0.000994 AC: 41 AN: 41266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25412

East Asian (EAS) AF: 0.00 AC: 0 AN: 37970

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099176

Other (OTH) AF: 0.0000169 AC: 1 AN: 59142

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000642

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.11	T
PhyloP100		-0.19
Sift4G	Benign	0.088	T
Vest4		0.015
gMVP		0.52

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: rs782350512; hg19: chr10-48438533;