rs76327447

Positions:

chr14-67761549-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015346.4(ZFYVE26):c.6405G>A(p.Leu2135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,614,160 control chromosomes in the GnomAD database, including 163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 146 hom. )

Consequence

ZFYVE26
NM_015346.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.319

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 14-67761549-C-T is Benign according to our data. Variant chr14-67761549-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 313880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-67761549-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.319 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZFYVE26	NM_015346.4 linkuse as main transcript	c.6405G>A	p.Leu2135=	synonymous_variant	35/42	ENST00000347230.9	NP_056161.2
ZFYVE26	XM_047431173.1 linkuse as main transcript	c.6405G>A	p.Leu2135=	synonymous_variant	35/42		XP_047287129.1
ZFYVE26	XM_047431174.1 linkuse as main transcript	c.4080G>A	p.Leu1360=	synonymous_variant	24/31		XP_047287130.1
ZFYVE26	XM_047431175.1 linkuse as main transcript	c.3987G>A	p.Leu1329=	synonymous_variant	24/31		XP_047287131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE26	ENST00000347230.9 linkuse as main transcript	c.6405G>A	p.Leu2135=	synonymous_variant	35/42	1	NM_015346.4	ENSP00000251119	P1

Frequencies

GnomAD3 genomes

AF:

0.00313

AC:

476

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0789

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00605

AC:

1520

AN:

251136

Hom.:

AF XY:

0.00550

AC XY:

746

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.0758

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00266

AC:

3887

AN:

1461858

Hom.:

146

Cov.:

AF XY:

0.00260

AC XY:

1891

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00149

Gnomad4 EAS exome

AF:

0.0801

Gnomad4 SAS exome

AF:

0.00129

Gnomad4 FIN exome

AF:

0.000974

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.00450

GnomAD4 genome

AF:

0.00312

AC:

475

AN:

152302

Hom.:

Cov.:

AF XY:

0.00355

AC XY:

264

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0787

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.000691

Hom.:

Bravo

AF:

0.00345

Asia WGS

AF:

0.0330

AC:

117

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2022	See Variant Classification Assertion Criteria. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary spastic paraplegia 15

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 29, 2015

- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Aug 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.0

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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