rs16877836

Positions:

• chr5-80477313-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000505560.5(ZFYVE16):​c.4556C>A​(p.Thr1519Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000981 in 1,609,346 control chromosomes in the GnomAD database, including 12 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0050 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (3 hom.)
• Consequence: ZFYVE16 ENST00000505560.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

Genes affected

ZFYVE16 (HGNC:20756): (zinc finger FYVE-type containing 16) This gene encodes an endosomal protein that belongs to the FYVE zinc finger family of proteins. The encoded protein is thought to regulate membrane trafficking in the endosome. This protein functions as a scaffold protein in the transforming growth factor-beta signaling pathway and is involved in positive and negative feedback regulation of the bone morphogenetic protein signaling pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

FAM151B-DT (HGNC:55578): (FAM151B divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006481111).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00502 (764/152094) while in subpopulation AFR AF= 0.0171 (708/41478). AF 95% confidence interval is 0.016. There are 9 homozygotes in gnomad4. There are 349 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE16	NM_001284236.3	c.4556C>A	p.Thr1519Asn	missense_variant	19/19	ENST00000505560.5	NP_001271165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE16	ENST00000505560.5	c.4556C>A	p.Thr1519Asn	missense_variant	19/19	1	NM_001284236.3	ENSP00000426848	P1
FAM151B-DT	ENST00000666568.1	n.258+8153G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00503 AC: 765 AN: 151976 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00127 AC: 313 AN: 246718 Hom.: 0 AF XY: 0.000808 AC XY: 108 AN XY: 133646

Gnomad AFR exome AF: 0.0164

Gnomad AMR exome AF: 0.000658

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000366

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.00100

GnomAD4 exome AF: 0.000559 AC: 815 AN: 1457252 Hom.: 3 Cov.: 32 AF XY: 0.000476 AC XY: 345 AN XY: 725046

Gnomad4 AFR exome AF: 0.0177

Gnomad4 AMR exome AF: 0.000796

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000397

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000666

Gnomad4 OTH exome AF: 0.00123

GnomAD4 genome AF: 0.00502 AC: 764 AN: 152094 Hom.: 9 Cov.: 32 AF XY: 0.00469 AC XY: 349 AN XY: 74350

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.00210

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00102 Hom.: 1

Bravo AF: 0.00589

ESP6500AA AF: 0.0182 AC: 80

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00166 AC: 201

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0097	T;T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	.;.;D
MetaRNN	Benign	0.0065	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M;M;M
MutationTaster	Benign	0.90	D;D;D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.053
Sift	Uncertain	0.027	D;D;D
Sift4G	Uncertain	0.030	D;D;D
Polyphen		0.92	P;P;P
Vest4		0.36
MVP		0.61
MPC		0.28
ClinPred		0.015	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.30

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: rs16877836; hg19: chr5-79773132;