3-192143732-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004113.6(FGF12):c.*277T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 322,996 control chromosomes in the GnomAD database, including 74,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (31154 hom., cov: 32)
  • Exomes 𝑓: 0.70 (42931 hom.)
• Consequence: FGF12 NM_004113.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.234

Genes affected

FGF12 (HGNC:3668): (fibroblast growth factor 12) 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 growth factor lacks the N-terminal signal sequence present in most of the FGF family members, but it contains clusters of basic residues that have been demonstrated to act as a nuclear localization signal. When transfected into mammalian cells, this protein accumulated in the nucleus, but was not secreted. The specific function of this gene has not yet been determined. [provided by RefSeq, Dec 2019]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 3-192143732-A-G is Benign according to our data. Variant chr3-192143732-A-G is described in ClinVar as [Benign]. Clinvar id is 1245924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF12	NM_004113.6	c.*277T>C		3_prime_UTR_variant	6/6	ENST00000445105.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF12	ENST00000445105.7	c.*277T>C		3_prime_UTR_variant	6/6	1	NM_004113.6	A1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94575 AN: 151844 Hom.: 31137 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.635

GnomAD4 exome AF: 0.695 AC: 118878 AN: 171034 Hom.: 42931 Cov.: 0 AF XY: 0.698 AC XY: 61372 AN XY: 87984

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.506

Gnomad4 ASJ exome AF: 0.773

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.687

Gnomad4 FIN exome AF: 0.788

Gnomad4 NFE exome AF: 0.744

Gnomad4 OTH exome AF: 0.686

GnomAD4 genome AF: 0.623 AC: 94631 AN: 151962 Hom.: 31154 Cov.: 32 AF XY: 0.624 AC XY: 46366 AN XY: 74282

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.634

Alfa AF: 0.668 Hom.: 11692

Bravo AF: 0.591

Asia WGS AF: 0.527 AC: 1831 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.5
Dann	Benign	0.83

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

LitVar

Other links and lift over

dbSNP: rs1460922; hg19: chr3-191861521;