rs532644018

Variant names:

• chr5-80437047-G-A
• rs532644018
• NM_001284236.3:c.362G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001284236.3(ZFYVE16):​c.362G>A​(p.Arg121Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: ZFYVE16 NM_001284236.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29374933).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284236.3. 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
	ZFYVE16	NM_001284236.3	MANE Select	c.362G>A	p.Arg121Gln	missense	Exon 4 of 19	NP_001271165.2	Q7Z3T8-1
	ZFYVE16	NM_001105251.4		c.362G>A	p.Arg121Gln	missense	Exon 4 of 19	NP_001098721.2	Q7Z3T8-1
	ZFYVE16	NM_001349434.2		c.362G>A	p.Arg121Gln	missense	Exon 4 of 19	NP_001336363.2	Q7Z3T8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE16	ENST00000505560.5	TSL:1 MANE Select	c.362G>A	p.Arg121Gln	missense	Exon 4 of 19	ENSP00000426848.1	Q7Z3T8-1
	ZFYVE16	ENST00000338008.9	TSL:1	c.362G>A	p.Arg121Gln	missense	Exon 3 of 18	ENSP00000337159.5	Q7Z3T8-1
	ZFYVE16	ENST00000510158.5	TSL:1	c.362G>A	p.Arg121Gln	missense	Exon 4 of 19	ENSP00000423663.1	Q7Z3T8-1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251056 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 52 AN: 1461834 Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 20 AN XY: 727220

African (AFR) AF: 0.000478 AC: 16 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53402

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111994

Other (OTH) AF: 0.000166 AC: 10 AN: 60394

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74340

African (AFR) AF: 0.000241 AC: 10 AN: 41420

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000149 Hom.: 0

Bravo AF: 0.000110

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions as Germline

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	0.081
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.094	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.7
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.085	T
Polyphen		1.0	D
Vest4		0.26
MVP		0.70
MPC		0.064
ClinPred		0.30	T
GERP RS		5.3
Varity_R		0.11
gMVP		0.12
Mutation Taster		=100/0	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

dbSNP: rs532644018; hg19: chr5-79732866; COSMIC: COSV106476953; COSMIC: COSV106476953;