Genetic Variant ZFYVE21:c.*1C>T (chr14-103733019-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024071.4(ZFYVE21):c.*1C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,613,724 control chromosomes in the GnomAD database, including 123,724 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 0.42 ( 13638 hom., cov: 33)

Exomes 𝑓: 0.39 ( 110086 hom. )

Consequence

ZFYVE21
NM_024071.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.843

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE21	NM_024071.4 link	c.*1C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000311141.7	NP_076976.1	Q9BQ24-1
PPP1R13B	NM_015316.3 link	c.*2135G>A		downstream_gene_variant		ENST00000202556.14	NP_056131.2	Q96KQ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE21	ENST00000311141.7 link	c.*1C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_024071.4	ENSP00000310543.2		Q9BQ24-1
PPP1R13B	ENST00000202556.14 link	c.*2135G>A		downstream_gene_variant		1	NM_015316.3	ENSP00000202556.9		Q96KQ4

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63411

AN:

151996

Hom.:

13611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.303

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.389

GnomAD3 exomes

AF:

0.378

AC:

94896

AN:

251024

Hom.:

18647

AF XY:

0.369

AC XY:

50146

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.514

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.308

Gnomad EAS exome

AF:

0.379

Gnomad SAS exome

AF:

0.278

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.385

AC:

563137

AN:

1461610

Hom.:

110086

Cov.:

AF XY:

0.381

AC XY:

276836

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.503

Gnomad4 AMR exome

AF:

0.356

Gnomad4 ASJ exome

AF:

0.302

Gnomad4 EAS exome

AF:

0.362

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.427

Gnomad4 NFE exome

AF:

0.392

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.417

AC:

63489

AN:

152114

Hom.:

13638

Cov.:

AF XY:

0.414

AC XY:

30754

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.505

Gnomad4 AMR

AF:

0.350

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.371

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.437

Gnomad4 NFE

AF:

0.398

Gnomad4 OTH

AF:

0.390

Alfa

AF:

0.376

Hom.:

13995

Bravo

AF:

0.415

Asia WGS

AF:

0.332

AC:

1155

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.7

DANN

Benign

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over