14-67766358-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015346.4(ZFYVE26):​c.5880G>C​(p.Arg1960Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. R1960R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZFYVE26
NM_015346.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0990

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • hereditary spastic paraplegia 15
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17050993).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFYVE26NM_015346.4 linkc.5880G>C p.Arg1960Ser missense_variant Exon 32 of 42 ENST00000347230.9 NP_056161.2 Q68DK2-1
ZFYVE26XM_047431173.1 linkc.5880G>C p.Arg1960Ser missense_variant Exon 32 of 42 XP_047287129.1
ZFYVE26XM_047431174.1 linkc.3555G>C p.Arg1185Ser missense_variant Exon 21 of 31 XP_047287130.1
ZFYVE26XM_047431175.1 linkc.3462G>C p.Arg1154Ser missense_variant Exon 21 of 31 XP_047287131.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFYVE26ENST00000347230.9 linkc.5880G>C p.Arg1960Ser missense_variant Exon 32 of 42 1 NM_015346.4 ENSP00000251119.5 Q68DK2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251278
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460854
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
726724
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33446
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86204
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4932
European-Non Finnish (NFE)
AF:
0.00000360
AC:
4
AN:
1112004
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60288
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
14
DANN
Uncertain
0.98
DEOGEN2
Benign
0.010
.;T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.75
.;T
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.0
T
PhyloP100
-0.099
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.34
N;N
REVEL
Benign
0.11
Sift
Benign
0.56
T;T
Sift4G
Benign
0.25
T;T
Polyphen
0.0070
.;B
Vest4
0.47
MutPred
0.55
Gain of ubiquitination at K1963 (P = 0.0972);Gain of ubiquitination at K1963 (P = 0.0972);
MVP
0.15
MPC
0.19
ClinPred
0.12
T
GERP RS
2.7
gMVP
0.26
Mutation Taster
=90/10
polymorphism

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

Other links and lift over

dbSNP: rs751183425; hg19: chr14-68233075; API