dbSNP rs17104689: ZFYVE26:p.Gly408Gly (chr14-67805264-C-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015346.4(ZFYVE26):c.1224G>T(p.Gly408Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,614,060 control chromosomes in the GnomAD database, including 546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 192 hom., cov: 33)

Exomes 𝑓: 0.015 ( 354 hom. )

Consequence

ZFYVE26
NM_015346.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.0170

Publications

8 publications found

Variant links:

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

ZFYVE26 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 14-67805264-C-A is Benign according to our data. Variant chr14-67805264-C-A is described in ClinVar as Benign. ClinVar VariationId is 130776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.017 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0843 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.1224G>T	p.Gly408Gly	synonymous	Exon 8 of 42	NP_056161.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFYVE26	ENST00000347230.9	TSL:1 MANE Select	c.1224G>T	p.Gly408Gly	synonymous	Exon 8 of 42	ENSP00000251119.5	Q68DK2-1
ZFYVE26	ENST00000555452.1	TSL:1	c.1224G>T	p.Gly408Gly	synonymous	Exon 8 of 35	ENSP00000450603.1	G3V2D8
ZFYVE26	ENST00000554523.5	TSL:1	n.1361G>T		non_coding_transcript_exon	Exon 8 of 41

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5041

AN:

152188

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0863

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0123

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0522

Gnomad SAS

AF:

0.0159

Gnomad FIN

AF:

0.00725

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.0263

GnomAD2 exomes

AF:

0.0186

AC:

4670

AN:

250946

AF XY:

0.0170

show subpopulations

Gnomad AFR exome

AF:

0.0894

Gnomad AMR exome

AF:

0.00599

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.0510

Gnomad FIN exome

AF:

0.00573

Gnomad NFE exome

AF:

0.0123

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.0153

AC:

22337

AN:

1461754

Hom.:

354

Cov.:

AF XY:

0.0150

AC XY:

10932

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.0850

AC:

2846

AN:

33474

American (AMR)

AF:

0.00637

AC:

285

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00111

AC:

AN:

26134

East Asian (EAS)

AF:

0.0603

AC:

2394

AN:

39686

South Asian (SAS)

AF:

0.0158

AC:

1362

AN:

86230

European-Finnish (FIN)

AF:

0.00721

AC:

385

AN:

53406

Middle Eastern (MID)

AF:

0.00990

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0125

AC:

13910

AN:

1111956

Other (OTH)

AF:

0.0177

AC:

1069

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1394

2788

4182

5576

6970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

612

1224

1836

2448

3060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0333

AC:

5069

AN:

152306

Hom.:

192

Cov.:

AF XY:

0.0322

AC XY:

2401

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0866

AC:

3600

AN:

41548

American (AMR)

AF:

0.0123

AC:

188

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.0525

AC:

272

AN:

5178

South Asian (SAS)

AF:

0.0164

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00725

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0115

AC:

783

AN:

68032

Other (OTH)

AF:

0.0260

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

244

488

732

976

1220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0369

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.0117

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Hereditary spastic paraplegia 15 (2)

not provided (2)

Hereditary spastic paraplegia (1)

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

9.0

(source)

DANN

Benign

0.68

PhyloP100

-0.017

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over