14-67790366-T-C

Variant names:

• chr14-67790366-T-C
• rs10131048
• NM_015346.4:c.2755+206A>G

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.2755+206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,100 control chromosomes in the GnomAD database, including 31,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.64 (31613 hom., cov: 32)
• Consequence: ZFYVE26 NM_015346.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.38

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=-0.91).
• BP6: Variant 14-67790366-T-C is Benign according to our data. Variant chr14-67790366-T-C is described in ClinVar as [Benign]. Clinvar id is 1245410.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE26	NM_015346.4	c.2755+206A>G		intron_variant	Intron 15 of 41	ENST00000347230.9	NP_056161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE26	ENST00000347230.9	c.2755+206A>G		intron_variant	Intron 15 of 41	1	NM_015346.4	ENSP00000251119.5

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97071 AN: 151982 Hom.: 31588 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.639 AC: 97136 AN: 152100 Hom.: 31613 Cov.: 32 AF XY: 0.648 AC XY: 48180 AN XY: 74366

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.925

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.638

Alfa AF: 0.608 Hom.: 5488

Bravo AF: 0.635

Asia WGS AF: 0.811 AC: 2820 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.016
DANN	Benign	0.37

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: rs10131048; hg19: chr14-68257083;