chr5-44304996-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM4PP5_Moderate

The NM_004465.2(FGF10):​c.626A>G​(p.Ter209Trpext*?) variant causes a stop lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

FGF10
NM_004465.2 stop_lost

Scores

3
4

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.81
Variant links:
Genes affected
FGF10 (HGNC:3666): (fibroblast growth factor 10) 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 exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7. Studies of the mouse homolog of suggested that this gene is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of lim bud formation. This gene is also implicated to be a primary factor in the process of wound healing. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_004465.2 Downstream stopcodon found after 2 codons.
PP5
Variant 5-44304996-T-C is Pathogenic according to our data. Variant chr5-44304996-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3370503.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FGF10NM_004465.2 linkc.626A>G p.Ter209Trpext*? stop_lost Exon 3 of 3 ENST00000264664.5 NP_004456.1 O15520A0A7U3JW18
FGF10XM_005248264.5 linkc.626A>G p.Ter209Trpext*? stop_lost Exon 4 of 4 XP_005248321.1 O15520A0A7U3JW18

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FGF10ENST00000264664.5 linkc.626A>G p.Ter209Trpext*? stop_lost Exon 3 of 3 1 NM_004465.2 ENSP00000264664.4 O15520

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Interstitial lung disease specific to childhood Pathogenic:1
Sep 23, 2024
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.046
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
17
DANN
Benign
0.85
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Pathogenic
0.99
D
Vest4
0.15
GERP RS
5.9

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-44305098; API