5-80437434-G-A

Variant names:

• chr5-80437434-G-A
• rs113579736
• NM_001284236.3:c.749G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001284236.3(ZFYVE16):​c.749G>A​(p.Arg250Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,602,334 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (71 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (42 hom.)
• Consequence: ZFYVE16 NM_001284236.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.753
• Publications: 2 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0010974705).
• BP6: Variant 5-80437434-G-A is Benign according to our data. Variant chr5-80437434-G-A is described in ClinVar as Benign. ClinVar VariationId is 768011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

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.749G>A	p.Arg250Gln	missense	Exon 4 of 19	NP_001271165.2	Q7Z3T8-1
	ZFYVE16	NM_001105251.4		c.749G>A	p.Arg250Gln	missense	Exon 4 of 19	NP_001098721.2	Q7Z3T8-1
	ZFYVE16	NM_001349434.2		c.749G>A	p.Arg250Gln	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.749G>A	p.Arg250Gln	missense	Exon 4 of 19	ENSP00000426848.1	Q7Z3T8-1
	ZFYVE16	ENST00000338008.9	TSL:1	c.749G>A	p.Arg250Gln	missense	Exon 3 of 18	ENSP00000337159.5	Q7Z3T8-1
	ZFYVE16	ENST00000510158.5	TSL:1	c.749G>A	p.Arg250Gln	missense	Exon 4 of 19	ENSP00000423663.1	Q7Z3T8-1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2602 AN: 152042 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.00426 AC: 1018 AN: 238974 AF XY: 0.00314

Gnomad AFR exome AF: 0.0563

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00118

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000824

Gnomad OTH exome AF: 0.00368

GnomAD4 exome AF: 0.00159 AC: 2299 AN: 1450174 Hom.: 42 Cov.: 67 AF XY: 0.00136 AC XY: 979 AN XY: 720714

African (AFR) AF: 0.0553 AC: 1811 AN: 32778

American (AMR) AF: 0.00415 AC: 173 AN: 41726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25482

East Asian (EAS) AF: 0.000556 AC: 22 AN: 39602

South Asian (SAS) AF: 0.000106 AC: 9 AN: 84834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53048

Middle Eastern (MID) AF: 0.00211 AC: 12 AN: 5686

European-Non Finnish (NFE) AF: 0.0000343 AC: 38 AN: 1107248

Other (OTH) AF: 0.00392 AC: 234 AN: 59770

GnomAD4 genome AF: 0.0172 AC: 2619 AN: 152160 Hom.: 71 Cov.: 32 AF XY: 0.0166 AC XY: 1236 AN XY: 74384

African (AFR) AF: 0.0579 AC: 2405 AN: 41508

American (AMR) AF: 0.0105 AC: 160 AN: 15284

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

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67974

Other (OTH) AF: 0.0180 AC: 38 AN: 2114

Alfa AF: 0.00718 Hom.: 54

Bravo AF: 0.0209

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0600 AC: 264

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00512 AC: 622

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.081
DEOGEN2	Benign	0.00040	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.8	N
PhyloP100		0.75
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	0.93	T
Polyphen		0.0	B
Vest4		0.070
MVP		0.19
MPC		0.050
ClinPred		0.0013	T
GERP RS		5.1
Varity_R		0.029
gMVP		0.045
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: rs113579736; hg19: chr5-79733253; COSMIC: COSV100566345; COSMIC: COSV100566345;