chr13-101721572-G-A

Position:

• chr13-101721572-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_004115.4(FGF14):​c.*1259C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 152,188 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: FGF14 NM_004115.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.857

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]

ENSG00000276012 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 13-101721572-G-A is Benign according to our data. Variant chr13-101721572-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 310868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00353 (537/152188) while in subpopulation NFE AF= 0.0061 (415/67996). AF 95% confidence interval is 0.00562. There are 2 homozygotes in gnomad4. There are 230 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 537 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF14	NM_004115.4	c.*1259C>T		3_prime_UTR_variant	5/5	ENST00000376143.5	NP_004106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF14	ENST00000376143	c.*1259C>T		3_prime_UTR_variant	5/5	1	NM_004115.4	ENSP00000365313.4

Frequencies

GnomAD3 genomes AF: 0.00354 AC: 538 AN: 152072 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00610

Gnomad OTH AF: 0.00383

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.00353 AC: 537 AN: 152188 Hom.: 2 Cov.: 32 AF XY: 0.00309 AC XY: 230 AN XY: 74404

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.00610

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00418 Hom.: 0

Bravo AF: 0.00330

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

FGF14: BS1, BS2 -

Spinocerebellar ataxia type 27 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	2.2
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs535930764; hg19: chr13-102373922;