chr13-102196915-T-C

Variant names:

• chr13-102196915-T-C
• rs544434
• ENST00000376131.9:c.208+204556A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175929.3(FGF14):​c.208+204556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 151,842 control chromosomes in the GnomAD database, including 1,628 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.080 (1628 hom., cov: 32)
• Consequence: FGF14 NM_175929.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• 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: Orphanet, Ambry Genetics
• autosomal recessive cerebellar ataxia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175929.3. 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_175929.3		c.208+204556A>G		intron	N/A	NP_787125.1	Q92915-2
	FGF14	NM_001321939.2		c.208+204556A>G		intron	N/A	NP_001308868.1
	FGF14	NM_001321945.2		c.91+204556A>G		intron	N/A	NP_001308874.1	A0A9L9PXK7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	ENST00000376131.9	TSL:1	c.208+204556A>G		intron	N/A	ENSP00000365301.3	Q92915-2
	FGF14	ENST00000418923.3	TSL:3	c.91+204556A>G		intron	N/A	ENSP00000516414.1	A0A9L9PXK7
	FGF14	ENST00000706494.1		c.-60+169530A>G		intron	N/A	ENSP00000516417.1	A0A9L9PX77

Frequencies

GnomAD3 genomes AF: 0.0795 AC: 12069 AN: 151732 Hom.: 1623 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.0532

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

GnomAD4 genome AF: 0.0797 AC: 12106 AN: 151842 Hom.: 1628 Cov.: 32 AF XY: 0.0765 AC XY: 5678 AN XY: 74242

African (AFR) AF: 0.276 AC: 11402 AN: 41268

American (AMR) AF: 0.0297 AC: 454 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00116 AC: 79 AN: 67998

Other (OTH) AF: 0.0527 AC: 111 AN: 2108

Alfa AF: 0.0500 Hom.: 282

Bravo AF: 0.0916

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.74
PhyloP100		-0.36
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: rs544434; hg19: chr13-102849265;