14-67767822-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015346.4(ZFYVE26):​c.5672A>C​(p.Asn1891Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. N1891S) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

ZFYVE26
NM_015346.4 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.377
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04229358).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFYVE26NM_015346.4 linkc.5672A>C p.Asn1891Thr missense_variant Exon 31 of 42 ENST00000347230.9 NP_056161.2 Q68DK2-1
ZFYVE26XM_047431173.1 linkc.5672A>C p.Asn1891Thr missense_variant Exon 31 of 42 XP_047287129.1
ZFYVE26XM_047431174.1 linkc.3347A>C p.Asn1116Thr missense_variant Exon 20 of 31 XP_047287130.1
ZFYVE26XM_047431175.1 linkc.3254A>C p.Asn1085Thr missense_variant Exon 20 of 31 XP_047287131.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFYVE26ENST00000347230.9 linkc.5672A>C p.Asn1891Thr missense_variant Exon 31 of 42 1 NM_015346.4 ENSP00000251119.5 Q68DK2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
68
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.66
DANN
Benign
0.60
DEOGEN2
Benign
0.0027
.;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.11
.;T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.042
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.32
T
PROVEAN
Benign
0.060
N;N
REVEL
Benign
0.0020
Sift
Benign
0.49
T;T
Sift4G
Benign
0.50
T;T
Polyphen
0.0
.;B
Vest4
0.056
MutPred
0.26
Gain of glycosylation at N1891 (P = 0.0148);Gain of glycosylation at N1891 (P = 0.0148);
MVP
0.061
MPC
0.16
ClinPred
0.018
T
GERP RS
-2.7
gMVP
0.12

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.

Other links and lift over

dbSNP: rs3742883; hg19: chr14-68234539; API