chr15-49424377-C-G

Variant names:

• chr15-49424377-C-G
• NM_002009.4:c.80C>G

Variant summary

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

The NM_002009.4(FGF7):​c.80C>G​(p.Thr27Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FGF7 NM_002009.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99
• Publications: 0 publications found

Genes affected

FGF7 (HGNC:3685): (fibroblast growth factor 7) 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 a potent epithelial cell-specific growth factor, whose mitogenic activity is predominantly exhibited in keratinocytes but not in fibroblasts and endothelial cells. Studies of mouse and rat homologs of this gene implicated roles in morphogenesis of epithelium, reepithelialization of wounds, hair development and early lung organogenesis. [provided by RefSeq, Jul 2008]

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

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=0.15403327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF7	NM_002009.4	c.80C>G	p.Thr27Ser	missense_variant	Exon 2 of 4	ENST00000267843.9	NP_002000.1
FAM227B	NM_152647.3	c.1013-52978G>C		intron_variant	Intron 11 of 15	ENST00000299338.11	NP_689860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF7	ENST00000267843.9	c.80C>G	p.Thr27Ser	missense_variant	Exon 2 of 4	1	NM_002009.4	ENSP00000267843.4
FAM227B	ENST00000299338.11	c.1013-52978G>C		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.80C>G (p.T27S) alteration is located in exon 2 (coding exon 1) of the FGF7 gene. This alteration results from a C to G substitution at nucleotide position 80, causing the threonine (T) at amino acid position 27 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.34	T;T;.
Eigen	Benign	0.058
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.67	.;T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N;N
PhyloP100		6.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.28	N;.;N
REVEL	Benign	0.072
Sift	Benign	0.53	T;.;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.0050	B;B;.
Vest4		0.10
MutPred		0.44		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.44
MPC		0.78
ClinPred		0.53	D
GERP RS		5.7
Varity_R		0.095
gMVP		0.31

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

hg19: chr15-49716574;