chr13-102173729-A-G

Variant names:

• chr13-102173729-A-G
• rs9554852
• ENST00000376131.9:c.208+227742T>C

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+227742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 152,232 control chromosomes in the GnomAD database, including 2,073 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 0.10 (2073 hom., cov: 32)
• Consequence: FGF14 NM_175929.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.858
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 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+227742T>C		intron	N/A	NP_787125.1	Q92915-2
	FGF14	NM_001321939.2		c.208+227742T>C		intron	N/A	NP_001308868.1
	FGF14	NM_001321945.2		c.91+227742T>C		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+227742T>C		intron	N/A	ENSP00000365301.3	Q92915-2
	FGF14	ENST00000418923.3	TSL:3	c.91+227742T>C		intron	N/A	ENSP00000516414.1	A0A9L9PXK7
	FGF14	ENST00000706494.1		c.-60+192716T>C		intron	N/A	ENSP00000516417.1	A0A9L9PX77

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15178 AN: 152112 Hom.: 2062 Cov.: 32

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.0912

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.0971

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

GnomAD4 genome AF: 0.0998 AC: 15198 AN: 152232 Hom.: 2073 Cov.: 32 AF XY: 0.110 AC XY: 8175 AN XY: 74428

African (AFR) AF: 0.0540 AC: 2247 AN: 41576

American (AMR) AF: 0.174 AC: 2664 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3472

East Asian (EAS) AF: 0.702 AC: 3620 AN: 5156

South Asian (SAS) AF: 0.295 AC: 1423 AN: 4818

European-Finnish (FIN) AF: 0.0912 AC: 968 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0564 AC: 3832 AN: 68002

Other (OTH) AF: 0.105 AC: 221 AN: 2114

Alfa AF: 0.0847 Hom.: 178

Bravo AF: 0.104

Asia WGS AF: 0.451 AC: 1563 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.78
PhyloP100		0.86
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: rs9554852; hg19: chr13-102826079;