dbSNP rs8548: ZFYVE21:n.4032A>C (chr14-103733243-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000555501.1(ZFYVE21):n.4032A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 574,164 control chromosomes in the GnomAD database, including 27,315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6493 hom., cov: 33)

Exomes 𝑓: 0.30 ( 20822 hom. )

Consequence

ZFYVE21
ENST00000555501.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.589

Publications

17 publications found

Variant links:

Genes affected

ZFYVE21 (HGNC:20760): (zinc finger FYVE-type containing 21) Predicted to enable metal ion binding activity. Predicted to be located in endosome and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ZFYVE21 links:

PPP1R13B (HGNC:14950): (protein phosphatase 1 regulatory subunit 13B) This gene encodes a member of the ASPP (apoptosis-stimulating protein of p53) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. ASPP proteins are required for the induction of apoptosis by p53-family proteins. They promote DNA binding and transactivation of p53-family proteins on the promoters of proapoptotic genes. Expression of this gene is regulated by the E2F transcription factor. [provided by RefSeq, Jul 2008]

PPP1R13B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R13B	NM_015316.3 link	c.*1911T>G		3_prime_UTR_variant	Exon 17 of 17	ENST00000202556.14	NP_056131.2
ZFYVE21	NM_024071.4 link	c.*225A>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000311141.7	NP_076976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R13B	ENST00000202556.14 link	c.*1911T>G		3_prime_UTR_variant	Exon 17 of 17	1	NM_015316.3	ENSP00000202556.9
ZFYVE21	ENST00000311141.7 link	c.*225A>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_024071.4	ENSP00000310543.2

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41144

AN:

151072

Hom.:

6482

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.195

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.259

GnomAD4 exome

AF:

0.304

AC:

128650

AN:

422972

Hom.:

20822

Cov.:

AF XY:

0.299

AC XY:

66064

AN XY:

220922

show subpopulations

African (AFR)

AF:

0.112

AC:

1326

AN:

11828

American (AMR)

AF:

0.265

AC:

4336

AN:

16384

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

2754

AN:

12714

East Asian (EAS)

AF:

0.331

AC:

9292

AN:

28078

South Asian (SAS)

AF:

0.201

AC:

7954

AN:

39496

European-Finnish (FIN)

AF:

0.388

AC:

10539

AN:

27162

Middle Eastern (MID)

AF:

0.198

AC:

426

AN:

2152

European-Non Finnish (NFE)

AF:

0.326

AC:

85141

AN:

261084

Other (OTH)

AF:

0.286

AC:

6882

AN:

24074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

3914

7827

11741

15654

19568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.272

AC:

41171

AN:

151192

Hom.:

6493

Cov.:

AF XY:

0.272

AC XY:

20117

AN XY:

73860

show subpopulations

African (AFR)

AF:

0.116

AC:

4759

AN:

40880

American (AMR)

AF:

0.273

AC:

4168

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

780

AN:

3464

East Asian (EAS)

AF:

0.329

AC:

1702

AN:

5176

South Asian (SAS)

AF:

0.212

AC:

1015

AN:

4786

European-Finnish (FIN)

AF:

0.412

AC:

4335

AN:

10530

Middle Eastern (MID)

AF:

0.205

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.347

AC:

23510

AN:

67808

Other (OTH)

AF:

0.261

AC:

550

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1499

2998

4498

5997

7496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.314

Hom.:

5165

Bravo

AF:

0.252

Asia WGS

AF:

0.261

AC:

907

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.2

(source)

DANN

Benign

0.79

PhyloP100

0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over