rs775035762

Variant names:

• chr14-103727804-C-G
• rs775035762
• NM_024071.4:c.248C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-103727804-C-G
• chr14-103727804-C-T

Variant summary

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

The NM_024071.4(ZFYVE21):​c.248C>G​(p.Pro83Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,238 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P83L) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
• Consequence: ZFYVE21 NM_024071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.63

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

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 rank	MANE	Protein	UniProt
ZFYVE21	NM_024071.4	c.248C>G	p.Pro83Arg	missense_variant	Exon 3 of 7	ENST00000311141.7	NP_076976.1
ZFYVE21	NM_001198953.2	c.248C>G	p.Pro83Arg	missense_variant	Exon 3 of 8		NP_001185882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE21	ENST00000311141.7	c.248C>G	p.Pro83Arg	missense_variant	Exon 3 of 7	1	NM_024071.4	ENSP00000310543.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152238 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152238 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74378

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	0.0089	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.48	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.86	P;D
Vest4		0.61
MutPred		0.50		Gain of MoRF binding (P = 0.0014);Gain of MoRF binding (P = 0.0014);
MVP		0.36
MPC		1.0
ClinPred		0.97	D
GERP RS		4.1
Varity_R		0.22
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs775035762; hg19: chr14-104194141;