rs10143623

Positions:

• chr14-103720539-G-A
• chr14-103720539-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024071.4(ZFYVE21):​c.138+4560G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,014 control chromosomes in the GnomAD database, including 7,248 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 0.30 (7248 hom., cov: 31)
• Consequence: ZFYVE21 NM_024071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE21	NM_024071.4	c.138+4560G>A		intron_variant		ENST00000311141.7	NP_076976.1
ZFYVE21	NM_001198953.2	c.138+4560G>A		intron_variant			NP_001185882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE21	ENST00000311141.7	c.138+4560G>A		intron_variant		1	NM_024071.4	ENSP00000310543	P1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45211 AN: 151898 Hom.: 7246 Cov.: 31

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45214 AN: 152014 Hom.: 7248 Cov.: 31 AF XY: 0.291 AC XY: 21608 AN XY: 74304

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.0758

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.311

Alfa AF: 0.344 Hom.: 1886

Bravo AF: 0.292

Asia WGS AF: 0.123 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.25

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

Other links and lift over

dbSNP: rs10143623; hg19: chr14-104186876;