rs75060573

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001385875.1(ZFYVE27):c.378G>A(p.Lys126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 1,613,534 control chromosomes in the GnomAD database, including 822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 43 hom., cov: 33)

Exomes 𝑓: 0.030 ( 779 hom. )

Consequence

ZFYVE27
NM_001385875.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

ZFYVE27 (HGNC:26559): (zinc finger FYVE-type containing 27) This gene encodes a protein with several transmembrane domains, a Rab11-binding domain and a lipid-binding FYVE finger domain. The encoded protein appears to promote neurite formation. A mutation in this gene has been reported to be associated with hereditary spastic paraplegia, however the pathogenicity of the mutation, which may simply represent a polymorphism, is unclear. [provided by RefSeq, Mar 2010]

ZFYVE27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 10-97744838-G-A is Benign according to our data. Variant chr10-97744838-G-A is described in ClinVar as [Benign]. Clinvar id is 130786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-97744838-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.78 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0202 (3071/152392) while in subpopulation SAS AF= 0.0435 (210/4832). AF 95% confidence interval is 0.0386. There are 43 homozygotes in gnomad4. There are 1422 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3071 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE27	NM_001385875.1 linkuse as main transcript	c.378G>A	p.Lys126=	synonymous_variant	4/13	ENST00000684270.1	NP_001372804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE27	ENST00000684270.1 linkuse as main transcript	c.378G>A	p.Lys126=	synonymous_variant	4/13		NM_001385875.1	ENSP00000506975	A1	Q5T4F4-1

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

3073

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00571

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0434

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0317

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0234

AC:

5844

AN:

250064

Hom.:

115

AF XY:

0.0256

AC XY:

3454

AN XY:

135154

show subpopulations

Gnomad AFR exome

AF:

0.00422

Gnomad AMR exome

AF:

0.00849

Gnomad ASJ exome

AF:

0.0285

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0466

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.0298

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0299

AC:

43752

AN:

1461142

Hom.:

779

Cov.:

AF XY:

0.0305

AC XY:

22150

AN XY:

726780

show subpopulations

Gnomad4 AFR exome

AF:

0.00373

Gnomad4 AMR exome

AF:

0.00949

Gnomad4 ASJ exome

AF:

0.0271

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0473

Gnomad4 FIN exome

AF:

0.0139

Gnomad4 NFE exome

AF:

0.0322

Gnomad4 OTH exome

AF:

0.0284

GnomAD4 genome

AF:

0.0202

AC:

3071

AN:

152392

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

1422

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.00567

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0435

Gnomad4 FIN

AF:

0.0108

Gnomad4 NFE

AF:

0.0317

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0245

Hom.:

Bravo

AF:

0.0192

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0300

EpiControl

AF:

0.0291

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 02, 2016	- -

Hereditary spastic paraplegia 33

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 12, 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. -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.9

DANN

Benign

0.51

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

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