dbSNP rs145183291: ZFYVE26:c.2332+7delT (chr14-67797664-CA-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_015346.4(ZFYVE26):c.2332+7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,613,816 control chromosomes in the GnomAD database, including 355 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 82 hom., cov: 32)

Exomes 𝑓: 0.014 ( 273 hom. )

Consequence

ZFYVE26
NM_015346.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.296

Variant links:

Genes affected

ZFYVE26 (HGNC:20761): (zinc finger FYVE-type containing 26) This gene encodes a protein which contains a FYVE zinc finger binding domain. The presence of this domain is thought to target these proteins to membrane lipids through interaction with phospholipids in the membrane. Mutations in this gene are associated with autosomal recessive spastic paraplegia-15. [provided by RefSeq, Oct 2008]

ZFYVE26 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 14-67797664-CA-C is Benign according to our data. Variant chr14-67797664-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 313914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-67797664-CA-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE26	NM_015346.4 link	c.2332+7delT	splice_region_variant, intron_variant	Intron 12 of 41	ENST00000347230.9	NP_056161.2	Q68DK2-1
ZFYVE26	XM_047431173.1 link	c.2332+7delT	splice_region_variant, intron_variant	Intron 12 of 41		XP_047287129.1
ZFYVE26	XM_011536609.3 link	c.2332+7delT	splice_region_variant, intron_variant	Intron 12 of 25		XP_011534911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE26	ENST00000347230.9 link	c.2332+7delT		splice_region_variant, intron_variant	Intron 12 of 41	1	NM_015346.4	ENSP00000251119.5		Q68DK2-1

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3882

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0596

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00968

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0519

Gnomad SAS

AF:

0.0159

Gnomad FIN

AF:

0.00726

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.0169

AC:

4231

AN:

251080

Hom.:

AF XY:

0.0157

AC XY:

2130

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.0631

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.0514

Gnomad SAS exome

AF:

0.0154

Gnomad FIN exome

AF:

0.00579

Gnomad NFE exome

AF:

0.0123

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0145

AC:

21186

AN:

1461558

Hom.:

273

Cov.:

AF XY:

0.0144

AC XY:

10454

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.0582

Gnomad4 AMR exome

AF:

0.00537

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.0606

Gnomad4 SAS exome

AF:

0.0158

Gnomad4 FIN exome

AF:

0.00723

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0158

GnomAD4 genome

AF:

0.0256

AC:

3896

AN:

152258

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

1865

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0598

Gnomad4 AMR

AF:

0.00960

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.0522

Gnomad4 SAS

AF:

0.0162

Gnomad4 FIN

AF:

0.00726

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.00393

Hom.:

Bravo

AF:

0.0277

Asia WGS

AF:

0.0330

AC:

113

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.0115

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 27, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Spastic paraplegia

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary spastic paraplegia

Benign:1

Nov 11, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spastic Paraplegia, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Sep 30, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary spastic paraplegia 15

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over