rs75391113

Variant names:

• chr14-67807831-G-A
• rs75391113
• NM_015346.4:c.453C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015346.4(ZFYVE26):​c.453C>T​(p.Ser151Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,613,986 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (126 hom.)
• Consequence: ZFYVE26 NM_015346.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.29
• Publications: 7 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), Orphanet, Myriad Women’s Health, G2P

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-67807831-G-A is Benign according to our data. Variant chr14-67807831-G-A is described in ClinVar as Benign. ClinVar VariationId is 313925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0673 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE26	NM_015346.4	MANE Select	c.453C>T	p.Ser151Ser	synonymous	Exon 5 of 42	NP_056161.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE26	ENST00000347230.9	TSL:1 MANE Select	c.453C>T	p.Ser151Ser	synonymous	Exon 5 of 42	ENSP00000251119.5
	ZFYVE26	ENST00000555452.1	TSL:1	c.453C>T	p.Ser151Ser	synonymous	Exon 5 of 35	ENSP00000450603.1
	ZFYVE26	ENST00000554523.5	TSL:1	n.590C>T		non_coding_transcript_exon	Exon 5 of 41

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 441 AN: 152142 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00569 AC: 1428 AN: 250864 AF XY: 0.00524

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.0722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00237 AC: 3465 AN: 1461726 Hom.: 126 Cov.: 32 AF XY: 0.00235 AC XY: 1709 AN XY: 727146

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00153 AC: 40 AN: 26108

East Asian (EAS) AF: 0.0712 AC: 2828 AN: 39696

South Asian (SAS) AF: 0.00130 AC: 112 AN: 86252

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53400

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.000192 AC: 213 AN: 1111912

Other (OTH) AF: 0.00414 AC: 250 AN: 60392

GnomAD4 genome AF: 0.00290 AC: 441 AN: 152260 Hom.: 12 Cov.: 32 AF XY: 0.00322 AC XY: 240 AN XY: 74432

African (AFR) AF: 0.000289 AC: 12 AN: 41546

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.0734 AC: 380 AN: 5178

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4828

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68012

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.000646 Hom.: 0

Bravo AF: 0.00324

Asia WGS AF: 0.0330 AC: 115 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary spastic paraplegia 15 (2)
-	-	2	not provided (2)
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.43
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs75391113; hg19: chr14-68274548; COSMIC: COSV61324584;