chr5-80438867-G-GA

Variant names:

• chr5-80438867-G-GA
• rs34397330
• NM_001284236.3:c.2186dupA

Variant summary

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

The NM_001284236.3(ZFYVE16):​c.2186dupA​(p.Asn729LysfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFYVE16 NM_001284236.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• 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: 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE16	NM_001284236.3	MANE Select	c.2186dupA	p.Asn729LysfsTer19	frameshift	Exon 4 of 19	NP_001271165.2
	ZFYVE16	NM_001105251.4		c.2186dupA	p.Asn729LysfsTer19	frameshift	Exon 4 of 19	NP_001098721.2
	ZFYVE16	NM_001349434.2		c.2186dupA	p.Asn729LysfsTer19	frameshift	Exon 4 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.2186dupA	p.Asn729LysfsTer19	frameshift	Exon 4 of 19	ENSP00000426848.1
	ZFYVE16	ENST00000338008.9	TSL:1	c.2186dupA	p.Asn729LysfsTer19	frameshift	Exon 3 of 18	ENSP00000337159.5
	ZFYVE16	ENST00000510158.5	TSL:1	c.2186dupA	p.Asn729LysfsTer19	frameshift	Exon 4 of 19	ENSP00000423663.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

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: rs34397330; hg19: chr5-79734686;