14-103715893-C-A

Variant names:

• chr14-103715893-C-A
• NM_024071.4:c.52C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024071.4(ZFYVE21):​c.52C>A​(p.Pro18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZFYVE21 NM_024071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34674248).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024071.4. 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
	ZFYVE21	NM_024071.4	MANE Select	c.52C>A	p.Pro18Thr	missense	Exon 1 of 7	NP_076976.1	Q9BQ24-1
	ZFYVE21	NM_001198953.2		c.52C>A	p.Pro18Thr	missense	Exon 1 of 8	NP_001185882.1	Q9BQ24-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE21	ENST00000311141.7	TSL:1 MANE Select	c.52C>A	p.Pro18Thr	missense	Exon 1 of 7	ENSP00000310543.2	Q9BQ24-1
	ZFYVE21	ENST00000944811.1		c.52C>A	p.Pro18Thr	missense	Exon 1 of 9	ENSP00000614870.1
	ZFYVE21	ENST00000892139.1		c.52C>A	p.Pro18Thr	missense	Exon 1 of 8	ENSP00000562198.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1288126 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 635990

African (AFR) AF: 0.00 AC: 0 AN: 25812

American (AMR) AF: 0.00 AC: 0 AN: 25342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21852

East Asian (EAS) AF: 0.00 AC: 0 AN: 26070

South Asian (SAS) AF: 0.00 AC: 0 AN: 71448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3842

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1022806

Other (OTH) AF: 0.00 AC: 0 AN: 51702

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.85	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.6
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.14
Sift	Benign	0.040	D
Sift4G	Benign	0.063	T
Polyphen		0.95	P
Vest4		0.21
MutPred		0.30		Gain of phosphorylation at P18 (P = 0.033)
MVP		0.26
MPC		0.67
ClinPred		0.78	D
GERP RS		2.4
PromoterAI		0.0012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.38
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

hg19: chr14-104182230;