rs10131048

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-67790366-T-C
• chr14-67790366-T-A
• chr14-67790366-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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), G2P, Orphanet, Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015346.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE26	NM_015346.4	MANE Select	c.2755+206A>G		intron	N/A	NP_056161.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE26	ENST00000347230.9	TSL:1 MANE Select	c.2755+206A>G		intron	N/A	ENSP00000251119.5	Q68DK2-1
	ZFYVE26	ENST00000555452.1	TSL:1	c.2755+206A>G		intron	N/A	ENSP00000450603.1	G3V2D8
	ZFYVE26	ENST00000554523.5	TSL:1	n.2892+206A>G		intron	N/A

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

African (AFR) AF: 0.563 AC: 23322 AN: 41458

American (AMR) AF: 0.727 AC: 11113 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1916 AN: 3468

East Asian (EAS) AF: 0.925 AC: 4789 AN: 5180

South Asian (SAS) AF: 0.751 AC: 3630 AN: 4832

European-Finnish (FIN) AF: 0.711 AC: 7532 AN: 10588

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.629 AC: 42748 AN: 67974

Other (OTH) AF: 0.638 AC: 1350 AN: 2116

Alfa AF: 0.607 Hom.: 5604

Bravo AF: 0.635

Asia WGS AF: 0.811 AC: 2820 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.016
DANN	Benign	0.37
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10131048; hg19: chr14-68257083;