chr13-102009157-C-T

Variant names:

• chr13-102009157-C-T
• rs16959573
• ENST00000376131.9:c.209-133861G>A

Variant summary

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

The NM_175929.3(FGF14):​c.209-133861G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 152,166 control chromosomes in the GnomAD database, including 606 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 0.049 (606 hom., cov: 33)
• Consequence: FGF14 NM_175929.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	NM_175929.3		c.209-133861G>A		intron	N/A	NP_787125.1
	FGF14	NM_001321939.2		c.209-140329G>A		intron	N/A	NP_001308868.1
	FGF14	NM_001321945.2		c.92-133861G>A		intron	N/A	NP_001308874.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	ENST00000376131.9	TSL:1	c.209-133861G>A		intron	N/A	ENSP00000365301.3
	FGF14	ENST00000418923.3	TSL:3	c.92-133861G>A		intron	N/A	ENSP00000516414.1
	FGF14	ENST00000706494.1		c.-59-133861G>A		intron	N/A	ENSP00000516417.1

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7492 AN: 152048 Hom.: 603 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0494 AC: 7517 AN: 152166 Hom.: 606 Cov.: 33 AF XY: 0.0480 AC XY: 3569 AN XY: 74404

African (AFR) AF: 0.170 AC: 7059 AN: 41498

American (AMR) AF: 0.0196 AC: 300 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 67986

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.0289 Hom.: 109

Bravo AF: 0.0583

Asia WGS AF: 0.00984 AC: 35 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		0.023
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: rs16959573; hg19: chr13-102661507;