rs12891047

Positions:

• chr14-67776358-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015346.4(ZFYVE26):​c.4975-252G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,014 control chromosomes in the GnomAD database, including 30,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.62 (30201 hom., cov: 32)
• Consequence: ZFYVE26 NM_015346.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.488

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 14-67776358-C-A is Benign according to our data. Variant chr14-67776358-C-A is described in ClinVar as [Benign]. Clinvar id is 669979.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE26	NM_015346.4	c.4975-252G>T		intron_variant		ENST00000347230.9	NP_056161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE26	ENST00000347230.9	c.4975-252G>T		intron_variant		1	NM_015346.4	ENSP00000251119	P1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94505 AN: 151896 Hom.: 30176 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.617

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.622 AC: 94568 AN: 152014 Hom.: 30201 Cov.: 32 AF XY: 0.632 AC XY: 47017 AN XY: 74338

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.622

Alfa AF: 0.630 Hom.: 46610

Bravo AF: 0.616

Asia WGS AF: 0.808 AC: 2811 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.35
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12891047; hg19: chr14-68243075;