chr10-101775209-G-T

Variant names:

• chr10-101775209-G-T
• NM_033163.5:c.77C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033163.5(FGF8):​c.77C>A​(p.Pro26Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,387,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 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. P26L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: FGF8 NM_033163.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854

Genes affected

FGF8 (HGNC:3686): (fibroblast growth factor 8) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein is known to be a factor that supports androgen and anchorage independent growth of mammary tumor cells. Overexpression of this gene has been shown to increase tumor growth and angiogensis. The adult expression of this gene is restricted to testes and ovaries. Temporal and spatial pattern of this gene expression suggests its function as an embryonic epithelial factor. Studies of the mouse and chick homologs revealed roles in midbrain and limb development, organogenesis, embryo gastrulation and left-right axis determination. The alternative splicing of this gene results in four transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17651433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF8	NM_033163.5	c.77C>A	p.Pro26Gln	missense_variant	Exon 3 of 6	ENST00000320185.7	NP_149353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF8	ENST00000320185.7	c.77C>A	p.Pro26Gln	missense_variant	Exon 3 of 6	1	NM_033163.5	ENSP00000321797.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000288 AC: 4 AN: 1387832 Hom.: 0 Cov.: 32 AF XY: 0.00000292 AC XY: 2 AN XY: 684482

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000373

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	0.0017	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Uncertain	0.48	T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.45	N;N
REVEL	Benign	0.28
Sift	Benign	0.34	T;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.19	B;B
Vest4		0.36
MutPred		0.30		Gain of solvent accessibility (P = 0.0055);Gain of solvent accessibility (P = 0.0055);
MVP		0.63
MPC		1.4
ClinPred		0.25	T
GERP RS		-0.41
Varity_R		0.056
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: 7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-103534966;