rs138607344

Variant names:

• chr13-101726640-T-A
• rs138607344
• NM_004115.4:c.579A>T

Your query was ambiguous. Multiple possible variants found:

• chr13-101726640-T-A
• chr13-101726640-T-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS1

The NM_175929.3(FGF14):​c.594A>T​(p.Ala198Ala) variant causes a synonymous change. The variant allele was found at a frequency of 0.000217 in 1,613,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: FGF14 NM_175929.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.98
• 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: Ambry Genetics, Orphanet
• autosomal recessive cerebellar ataxia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 13-101726640-T-A is Benign according to our data. Variant chr13-101726640-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 447328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000408 (62/152112) while in subpopulation AMR AF = 0.00275 (42/15250). AF 95% confidence interval is 0.00209. There are 0 homozygotes in GnomAd4. There are 43 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_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_004115.4	MANE Select	c.579A>T	p.Ala193Ala	synonymous	Exon 4 of 5	NP_004106.1
	FGF14	NM_175929.3		c.594A>T	p.Ala198Ala	synonymous	Exon 4 of 5	NP_787125.1
	FGF14	NM_001321939.2		c.483A>T	p.Ala161Ala	synonymous	Exon 3 of 4	NP_001308868.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF14	ENST00000376143.5	TSL:1 MANE Select	c.579A>T	p.Ala193Ala	synonymous	Exon 4 of 5	ENSP00000365313.4
	FGF14	ENST00000376131.9	TSL:1	c.594A>T	p.Ala198Ala	synonymous	Exon 4 of 5	ENSP00000365301.3
	FGF14	ENST00000418923.3	TSL:3	c.477A>T	p.Ala159Ala	synonymous	Exon 5 of 6	ENSP00000516414.1

Frequencies

GnomAD3 genomes AF: 0.000408 AC: 62 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000159 AC: 40 AN: 251132 AF XY: 0.000177

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000197 AC: 288 AN: 1461250 Hom.: 0 Cov.: 31 AF XY: 0.000204 AC XY: 148 AN XY: 726932

African (AFR) AF: 0.0000897 AC: 3 AN: 33440

American (AMR) AF: 0.000493 AC: 22 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000232 AC: 258 AN: 1111620

Other (OTH) AF: 0.0000663 AC: 4 AN: 60360

GnomAD4 genome AF: 0.000408 AC: 62 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.000579 AC XY: 43 AN XY: 74318

African (AFR) AF: 0.0000965 AC: 4 AN: 41450

American (AMR) AF: 0.00275 AC: 42 AN: 15250

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000226 Hom.: 0

Bravo AF: 0.000295

EpiCase AF: 0.000436

EpiControl AF: 0.000356

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	FGF14-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		5.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs138607344; hg19: chr13-102378990;