10-47300922-G-T

Variant names:

• chr10-47300922-G-T
• rs376019600
• NM_004962.5:c.271G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004962.5(GDF10):​c.271G>T​(p.Ala91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A91T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GDF10 NM_004962.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11154553).

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.271G>T	p.Ala91Ser	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.271G>T	p.Ala91Ser	missense	Exon 1 of 3	ENSP00000464145.1	P55107
	GDF10	ENST00000895678.1		c.271G>T	p.Ala91Ser	missense	Exon 1 of 3	ENSP00000565737.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000530 AC: 1 AN: 188690 AF XY: 0.00000951

Gnomad AFR exome AF: 0.0000954

Gnomad AMR exome AF: 0.00

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: 7.16e-7 AC: 1 AN: 1396724 Hom.: 0 Cov.: 34 AF XY: 0.00000145 AC XY: 1 AN XY: 690956

African (AFR) AF: 0.0000335 AC: 1 AN: 29808

American (AMR) AF: 0.00 AC: 0 AN: 39374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23816

East Asian (EAS) AF: 0.00 AC: 0 AN: 35900

South Asian (SAS) AF: 0.00 AC: 0 AN: 79286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5576

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086814

Other (OTH) AF: 0.00 AC: 0 AN: 58006

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000869 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_noAF	Benign	-0.54
CADD	Benign	10
DANN	Benign	0.88
DEOGEN2	Benign	0.22	T
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.11	T
PhyloP100		0.56
Sift4G	Benign	0.80	T
Vest4		0.054
gMVP		0.52
Mutation Taster		=100/0	polymorphism

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: rs376019600; hg19: chr10-48438440;