rs3742883

chr14-67767822-T-Achr14-67767822-T-Cchr14-67767822-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015346.4(ZFYVE26):c.5672A>T(p.Asn1891Ile) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07242203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFYVE26	NM_015346.4	c.5672A>T	p.Asn1891Ile	missense_variant	31/42	ENST00000347230.9
ZFYVE26	XM_047431173.1	c.5672A>T	p.Asn1891Ile	missense_variant	31/42
ZFYVE26	XM_047431174.1	c.3347A>T	p.Asn1116Ile	missense_variant	20/31
ZFYVE26	XM_047431175.1	c.3254A>T	p.Asn1085Ile	missense_variant	20/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFYVE26	ENST00000347230.9	c.5672A>T	p.Asn1891Ile	missense_variant	31/42	1	NM_015346.4	P1

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	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	3.3
Dann	Benign	0.70
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.71	N;N
REVEL	Benign	0.021
Sift	Benign	0.12	T;T
Sift4G	Uncertain	0.056	T;D
Polyphen		0.050	.;B
Vest4		0.29
MutPred		0.21		Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);
MVP		0.12
MPC		0.20
ClinPred		0.039	T
GERP RS		-2.7
gMVP		0.24

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

Other links and lift over

dbSNP: rs3742883; hg19: chr14-68234539;