Variant 1-52238103-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004799.4(ZFYVE9):c.686T>C(p.Leu229Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZFYVE9
NM_004799.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

ZFYVE9 (HGNC:6775): (zinc finger FYVE-type containing 9) This gene encodes a double zinc finger motif-containing protein that participates in the transforming growth factor-beta (TGFB) signalling pathway. The encoded protein interacts directly with SMAD2 and SMAD3, and recruits SMAD2 to the TGFB receptor. There are multiple pseudogenes for this gene on chromosomes 2, 15, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ZFYVE9 links:

ZFYVE9 (HGNC:):

ZFYVE9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11905855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE9	NM_004799.4 linkuse as main transcript	c.686T>C	p.Leu229Pro	missense_variant	4/19	ENST00000287727.8	NP_004790.2	O95405-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZFYVE9	ENST00000287727.8 linkuse as main transcript	c.686T>C	p.Leu229Pro	missense_variant	4/19	5	NM_004799.4	ENSP00000287727.3	O95405-1
ZFYVE9	ENST00000371591.2 linkuse as main transcript	c.686T>C	p.Leu229Pro	missense_variant	5/20	1		ENSP00000360647.1	O95405-1
ZFYVE9	ENST00000357206.6 linkuse as main transcript	c.686T>C	p.Leu229Pro	missense_variant	4/18	1		ENSP00000349737.2	O95405-2
ZFYVE9	ENST00000361625.5 linkuse as main transcript	n.858T>C		non_coding_transcript_exon_variant	4/5	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.686T>C (p.L229P) alteration is located in exon 4 (coding exon 2) of the ZFYVE9 gene. This alteration results from a T to C substitution at nucleotide position 686, causing the leucine (L) at amino acid position 229 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0090

T;.;T

Eigen

Benign

-0.056

Eigen_PC

Benign

-0.072

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.66

T;T;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.97

L;L;L

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0010

D;D;D

Sift4G

Benign

0.32

T;T;T

Polyphen

0.83

P;P;P

Vest4

0.58

MutPred

0.15

Loss of stability (P = 0.0506);Loss of stability (P = 0.0506);Loss of stability (P = 0.0506);

MVP

0.13

MPC

0.33

ClinPred

0.39

GERP RS

5.1

Varity_R

0.27

gMVP

0.33

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over