13-101721164-TGAG-T

Variant names:

• chr13-101721164-TGAG-T
• rs141424596
• NM_004115.4:c.*1664_*1666delCTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004115.4(FGF14):​c.*1664_*1666delCTC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 152,228 control chromosomes in the GnomAD database, including 209 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (209 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: FGF14 NM_004115.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.44
• Publications: 1 publications found

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]

FGF14 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia 27A

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• spinocerebellar ataxia type 27

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• autosomal recessive cerebellar ataxia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000276012 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 13-101721164-TGAG-T is Benign according to our data. Variant chr13-101721164-TGAG-T is described in ClinVar as [Likely_benign]. Clinvar id is 310862.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF14	NM_004115.4	c.*1664_*1666delCTC		3_prime_UTR_variant	Exon 5 of 5	ENST00000376143.5	NP_004106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF14	ENST00000376143.5	c.*1664_*1666delCTC		3_prime_UTR_variant	Exon 5 of 5	1	NM_004115.4	ENSP00000365313.4

Frequencies

GnomAD3 genomes AF: 0.0466 AC: 7094 AN: 152110 Hom.: 208 Cov.: 31

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0410

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.0803

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0615

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0464

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0467 AC: 7105 AN: 152228 Hom.: 209 Cov.: 31 AF XY: 0.0471 AC XY: 3507 AN XY: 74424

African (AFR) AF: 0.0190 AC: 791 AN: 41572

American (AMR) AF: 0.0409 AC: 624 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3470

East Asian (EAS) AF: 0.0805 AC: 415 AN: 5156

South Asian (SAS) AF: 0.0646 AC: 312 AN: 4826

European-Finnish (FIN) AF: 0.0615 AC: 653 AN: 10614

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0576 AC: 3916 AN: 67996

Other (OTH) AF: 0.0511 AC: 108 AN: 2114

Alfa AF: 0.0478 Hom.: 29

Bravo AF: 0.0431

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant cerebellar ataxia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs141424596; hg19: chr13-102373514;