rs138607344

chr13-101726640-T-Achr13-101726640-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_004115.4(FGF14):c.579A>T(p.Ala193=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000217 in 1,613,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: FGF14 NM_004115.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.98

Genes affected

FGF14 (HGNC:3671): (fibroblast growth factor 14) 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. A mutation in this gene is associated with autosomal dominant cerebral ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 13-101726640-T-A is Benign according to our data. Variant chr13-101726640-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 447328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF14	NM_004115.4	c.579A>T	p.Ala193=	synonymous_variant	4/5	ENST00000376143.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF14	ENST00000376143.5	c.579A>T	p.Ala193=	synonymous_variant	4/5	1	NM_004115.4	P2

Frequencies

GnomAD3 genomes AF: 0.000408 AC: 62 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000159 AC: 40 AN: 251132 Hom.: 0 AF XY: 0.000177 AC XY: 24 AN XY: 135738

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000197 AC: 288 AN: 1461250 Hom.: 0 Cov.: 31 AF XY: 0.000204 AC XY: 148 AN XY: 726932

Gnomad4 AFR exome AF: 0.0000897

Gnomad4 AMR exome AF: 0.000493

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000232

Gnomad4 OTH exome AF: 0.0000663

GnomAD4 genome AF: 0.000408 AC: 62 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.000579 AC XY: 43 AN XY: 74318

Gnomad4 AFR AF: 0.0000965

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000226 Hom.: 0

Bravo AF: 0.000295

EpiCase AF: 0.000436

EpiControl AF: 0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Sep 02, 2016

- -

FGF14-related condition Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 08, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	13
Dann	Benign	0.81

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: rs138607344; hg19: chr13-102378990;