13-101721218-CCAAA-C

Variant names:

• chr13-101721218-CCAAA-C
• rs747506157
• NM_004115.4:c.*1609_*1612delTTTG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_004115.4(FGF14):​c.*1609_*1612delTTTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 152,060 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: FGF14 NM_004115.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52
• Publications: 0 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

ENSG00000276012 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00025 (38/152060) while in subpopulation NFE AF = 0.000471 (32/67978). AF 95% confidence interval is 0.000342. There are 0 homozygotes in GnomAd4. There are 9 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.*1609_*1612delTTTG		3_prime_UTR	Exon 5 of 5	NP_004106.1	Q92915-1
	FGF14	NM_175929.3		c.*1609_*1612delTTTG		3_prime_UTR	Exon 5 of 5	NP_787125.1	Q92915-2
	FGF14	NM_001321939.2		c.*1609_*1612delTTTG		3_prime_UTR	Exon 4 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.*1609_*1612delTTTG		3_prime_UTR	Exon 5 of 5	ENSP00000365313.4	Q92915-1
	FGF14	ENST00000376131.9	TSL:1	c.*1609_*1612delTTTG		3_prime_UTR	Exon 5 of 5	ENSP00000365301.3	Q92915-2
	FGF14	ENST00000706491.1		n.*1957_*1960delTTTG		non_coding_transcript_exon	Exon 6 of 6	ENSP00000516413.1	A0A9L9PXI9

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 151942 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000471

Gnomad OTH AF: 0.000480

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

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152060 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74312

African (AFR) AF: 0.0000723 AC: 3 AN: 41504

American (AMR) AF: 0.0000656 AC: 1 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000471 AC: 32 AN: 67978

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000295

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal dominant cerebellar ataxia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

Splicing

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

Other links and lift over

dbSNP: rs747506157; hg19: chr13-102373568;