5-80449650-A-T

Variant names:

• chr5-80449650-A-T
• rs249038
• NM_001284236.3:c.3163A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001284236.3(ZFYVE16):​c.3163A>T​(p.Ser1055Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZFYVE16 NM_001284236.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 36 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.3163A>T	p.Ser1055Cys	missense	Exon 9 of 19	NP_001271165.2	Q7Z3T8-1
	ZFYVE16	NM_001105251.4		c.3163A>T	p.Ser1055Cys	missense	Exon 9 of 19	NP_001098721.2	Q7Z3T8-1
	ZFYVE16	NM_001349434.2		c.3163A>T	p.Ser1055Cys	missense	Exon 9 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.3163A>T	p.Ser1055Cys	missense	Exon 9 of 19	ENSP00000426848.1	Q7Z3T8-1
	ZFYVE16	ENST00000338008.9	TSL:1	c.3163A>T	p.Ser1055Cys	missense	Exon 8 of 18	ENSP00000337159.5	Q7Z3T8-1
	ZFYVE16	ENST00000510158.5	TSL:1	c.3163A>T	p.Ser1055Cys	missense	Exon 9 of 19	ENSP00000423663.1	Q7Z3T8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1457384 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 725076

African (AFR) AF: 0.00 AC: 0 AN: 33214

American (AMR) AF: 0.00 AC: 0 AN: 43812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39286

South Asian (SAS) AF: 0.00 AC: 0 AN: 85506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110228

Other (OTH) AF: 0.00 AC: 0 AN: 60194

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Benign	0.61
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.69	N
PhyloP100		2.5
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.097
Sift	Benign	0.12	T
Sift4G	Uncertain	0.042	D
Polyphen		0.26	B
Vest4		0.12
MutPred		0.45		Loss of glycosylation at T1060 (P = 0.1356)
MVP		0.43
MPC		0.058
ClinPred		0.39	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.091
gMVP		0.060
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.41		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs249038; hg19: chr5-79745469;