14-72977932-G-A

Position:

• chr14-72977932-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021260.4(ZFYVE1):​c.1630C>T​(p.Pro544Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFYVE1 NM_021260.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0

Genes affected

ZFYVE1 (HGNC:13180): (zinc finger FYVE-type containing 1) The FYVE domain mediates the recruitment of proteins involved in membrane trafficking and cell signaling to phosphatidylinositol 3-phosphate-containing membranes. This protein contains two zinc-binding FYVE domains in tandem and is reported to localize to the Golgi apparatus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE1	NM_021260.4	c.1630C>T	p.Pro544Ser	missense_variant	8/12	ENST00000556143.6	NP_067083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE1	ENST00000556143.6	c.1630C>T	p.Pro544Ser	missense_variant	8/12	1	NM_021260.4	ENSP00000450742	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.1630C>T (p.P544S) alteration is located in exon 8 (coding exon 7) of the ZFYVE1 gene. This alteration results from a C to T substitution at nucleotide position 1630, causing the proline (P) at amino acid position 544 to be replaced by a serine (S). 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	0.14
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.029	T;.;T;.;.
Eigen	Uncertain	0.61
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;.;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.50	T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.2	.;.;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.4	N;N;N;D;D
REVEL	Uncertain	0.33
Sift	Benign	0.15	T;T;T;T;T
Sift4G	Benign	0.079	T;T;T;T;T
Polyphen		0.72	P;.;P;.;.
Vest4		0.75
MutPred		0.51		Gain of relative solvent accessibility (P = 0.0479);.;Gain of relative solvent accessibility (P = 0.0479);.;.;
MVP		0.20
MPC		1.1
ClinPred		0.94	D
GERP RS		6.2
Varity_R		0.24
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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.

Other links and lift over

hg19: chr14-73444640;