rs10893385

Variant names:

• chr11-125479025-A-G
• rs10893385
• NM_005103.5:c.411+2509T>C

Variant summary

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

The NM_005103.5(FEZ1):​c.411+2509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,970 control chromosomes in the GnomAD database, including 18,215 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 0.47 (18215 hom., cov: 32)
• Consequence: FEZ1 NM_005103.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 7 publications found

Genes affected

FEZ1 (HGNC:3659): (fasciculation and elongation protein zeta 1) This gene is an ortholog of the C. elegans unc-76 gene, which is necessary for normal axonal bundling and elongation within axon bundles. Expression of this gene in C. elegans unc-76 mutants can restore to the mutants partial locomotion and axonal fasciculation, suggesting that it also functions in axonal outgrowth. The N-terminal half of the gene product is highly acidic. Alternatively spliced transcript variants encoding different isoforms of this protein have been described. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005103.5. 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
	FEZ1	NM_005103.5	MANE Select	c.411+2509T>C		intron	N/A	NP_005094.1	Q99689-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEZ1	ENST00000278919.8	TSL:1 MANE Select	c.411+2509T>C		intron	N/A	ENSP00000278919.3	Q99689-1
	FEZ1	ENST00000965005.1		c.462+726T>C		intron	N/A	ENSP00000635064.1
	FEZ1	ENST00000863680.1		c.411+2509T>C		intron	N/A	ENSP00000533739.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72066 AN: 151852 Hom.: 18219 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.474 AC: 72075 AN: 151970 Hom.: 18215 Cov.: 32 AF XY: 0.476 AC XY: 35333 AN XY: 74270

African (AFR) AF: 0.293 AC: 12160 AN: 41446

American (AMR) AF: 0.612 AC: 9347 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1786 AN: 3470

East Asian (EAS) AF: 0.620 AC: 3195 AN: 5152

South Asian (SAS) AF: 0.615 AC: 2959 AN: 4814

European-Finnish (FIN) AF: 0.434 AC: 4585 AN: 10556

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36446 AN: 67952

Other (OTH) AF: 0.491 AC: 1039 AN: 2114

Alfa AF: 0.523 Hom.: 7598

Bravo AF: 0.479

Asia WGS AF: 0.560 AC: 1948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.028
DANN	Benign	0.24
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs10893385; hg19: chr11-125348921;