chr5-80477313-C-A

Variant names:

• chr5-80477313-C-A
• rs16877836
• NM_001284236.3:c.4556C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001284236.3(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.

• Frequency:
  • Genomes: 𝑓 0.0050 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (3 hom.)
• Consequence: ZFYVE16 NM_001284236.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 6 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 -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE16	NM_001284236.3	MANE Select	c.4556C>A	p.Thr1519Asn	missense	Exon 19 of 19	NP_001271165.2
	ZFYVE16	NM_001105251.4		c.4556C>A	p.Thr1519Asn	missense	Exon 19 of 19	NP_001098721.2
	ZFYVE16	NM_001349434.2		c.4556C>A	p.Thr1519Asn	missense	Exon 19 of 19	NP_001336363.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE16	ENST00000505560.5	TSL:1 MANE Select	c.4556C>A	p.Thr1519Asn	missense	Exon 19 of 19	ENSP00000426848.1
	ZFYVE16	ENST00000338008.9	TSL:1	c.4556C>A	p.Thr1519Asn	missense	Exon 18 of 18	ENSP00000337159.5
	ZFYVE16	ENST00000510158.5	TSL:1	c.4556C>A	p.Thr1519Asn	missense	Exon 19 of 19	ENSP00000423663.1

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

GnomAD2 exomes AF: 0.00127 AC: 313 AN: 246718 AF XY: 0.000808

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 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

African (AFR) AF: 0.0177 AC: 587 AN: 33112

American (AMR) AF: 0.000796 AC: 35 AN: 43974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39308

South Asian (SAS) AF: 0.000397 AC: 34 AN: 85726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52698

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5752

European-Non Finnish (NFE) AF: 0.0000666 AC: 74 AN: 1110416

Other (OTH) AF: 0.00123 AC: 74 AN: 60206

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

African (AFR) AF: 0.0171 AC: 708 AN: 41478

American (AMR) AF: 0.00210 AC: 32 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67980

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00183 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 v4.9

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
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
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.0
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.053
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.030	D
Polyphen		0.92	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
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: rs16877836; hg19: chr5-79773132;