NM_004115.4:c.487delA

Variant names:

• chr13-101726731-CT-C
• rs587776685
• NM_004115.4:c.487delA

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_004115.4(FGF14):​c.487delA​(p.Arg163AspfsTer13) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FGF14 NM_004115.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.90
• Publications: 5 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: Orphanet, Ambry Genetics
• autosomal recessive cerebellar ataxia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-101726731-CT-C is Pathogenic according to our data. Variant chr13-101726731-CT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 8116.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004115.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	NM_004115.4	MANE Select	c.487delA	p.Arg163AspfsTer13	frameshift	Exon 4 of 5	NP_004106.1	Q92915-1
	FGF14	NM_175929.3		c.502delA	p.Arg168AspfsTer13	frameshift	Exon 4 of 5	NP_787125.1	Q92915-2
	FGF14	NM_001321939.2		c.391delA	p.Arg131AspfsTer13	frameshift	Exon 3 of 4	NP_001308868.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	ENST00000376143.5	TSL:1 MANE Select	c.487delA	p.Arg163AspfsTer13	frameshift	Exon 4 of 5	ENSP00000365313.4	Q92915-1
	FGF14	ENST00000376131.9	TSL:1	c.502delA	p.Arg168AspfsTer13	frameshift	Exon 4 of 5	ENSP00000365301.3	Q92915-2
	FGF14	ENST00000418923.3	TSL:3	c.385delA	p.Arg129AspfsTer13	frameshift	Exon 5 of 6	ENSP00000516414.1	A0A9L9PXK7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Spinocerebellar ataxia 27A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9
Mutation Taster		=3/197	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

dbSNP: rs587776685; hg19: chr13-102379081;