11-125443703-A-G

Variant names:

• chr11-125443703-A-G
• rs7930295
• NM_005103.5:c.*2392T>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.*2392T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,164 control chromosomes in the GnomAD database, including 1,614 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 0.14 (1614 hom., cov: 32)
• Consequence: FEZ1 NM_005103.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 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.*2392T>C		3_prime_UTR	Exon 10 of 10	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.*2392T>C		3_prime_UTR	Exon 10 of 10	ENSP00000278919.3	Q99689-1
	FEZ1	ENST00000648911.1		c.*2392T>C		3_prime_UTR	Exon 12 of 12	ENSP00000497070.1	Q99689-1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21252 AN: 152046 Hom.: 1614 Cov.: 32

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.140 AC: 21255 AN: 152164 Hom.: 1614 Cov.: 32 AF XY: 0.141 AC XY: 10524 AN XY: 74382

African (AFR) AF: 0.0969 AC: 4024 AN: 41542

American (AMR) AF: 0.144 AC: 2204 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3466

East Asian (EAS) AF: 0.281 AC: 1451 AN: 5168

South Asian (SAS) AF: 0.160 AC: 769 AN: 4812

European-Finnish (FIN) AF: 0.173 AC: 1834 AN: 10594

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10079 AN: 67988

Other (OTH) AF: 0.142 AC: 300 AN: 2108

Alfa AF: 0.145 Hom.: 2780

Bravo AF: 0.136

Asia WGS AF: 0.190 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.35
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs7930295; hg19: chr11-125313599;