chr5-80437449-T-C

Variant names:

• chr5-80437449-T-C
• rs1750092319
• NM_001284236.3:c.764T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001284236.3(ZFYVE16):​c.764T>C​(p.Met255Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,449,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ZFYVE16 NM_001284236.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.88
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029630959).

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.764T>C	p.Met255Thr	missense	Exon 4 of 19	NP_001271165.2	Q7Z3T8-1
	ZFYVE16	NM_001105251.4		c.764T>C	p.Met255Thr	missense	Exon 4 of 19	NP_001098721.2	Q7Z3T8-1
	ZFYVE16	NM_001349434.2		c.764T>C	p.Met255Thr	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.764T>C	p.Met255Thr	missense	Exon 4 of 19	ENSP00000426848.1	Q7Z3T8-1
	ZFYVE16	ENST00000338008.9	TSL:1	c.764T>C	p.Met255Thr	missense	Exon 3 of 18	ENSP00000337159.5	Q7Z3T8-1
	ZFYVE16	ENST00000510158.5	TSL:1	c.764T>C	p.Met255Thr	missense	Exon 4 of 19	ENSP00000423663.1	Q7Z3T8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000621 AC: 9 AN: 1449670 Hom.: 0 Cov.: 67 AF XY: 0.00000555 AC XY: 4 AN XY: 720406

African (AFR) AF: 0.0000917 AC: 3 AN: 32732

American (AMR) AF: 0.00 AC: 0 AN: 41572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25472

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.00 AC: 0 AN: 84972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1106838

Other (OTH) AF: 0.0000167 AC: 1 AN: 59748

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

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	0.10
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.094
DANN	Benign	0.29
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.090	N
PhyloP100		-1.9
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.0030
Sift	Benign	0.61	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.032
MutPred		0.24		Gain of loop (P = 0.0166)
MVP		0.13
MPC		0.050
ClinPred		0.014	T
GERP RS		-2.1
Varity_R		0.077
gMVP		0.052
Mutation Taster		=98/2	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: rs1750092319; hg19: chr5-79733268;