14-72974819-C-G

Variant names:

• chr14-72974819-C-G
• NM_021260.4:c.1947G>C
• ZFYVE1 p.Arg649Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_021260.4(ZFYVE1):​c.1947G>C​(p.Arg649Arg) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFYVE1 NM_021260.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 0 publications found

Genes affected

ZFYVE1 (HGNC:13180): (zinc finger FYVE-type containing 1) The FYVE domain mediates the recruitment of proteins involved in membrane trafficking and cell signaling to phosphatidylinositol 3-phosphate-containing membranes. This protein contains two zinc-binding FYVE domains in tandem and is reported to localize to the Golgi apparatus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-2.01 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021260.4. 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
	ZFYVE1	NM_021260.4	MANE Select	c.1947G>C	p.Arg649Arg	synonymous	Exon 10 of 12	NP_067083.1	Q9HBF4-1
	ZFYVE1	NM_001281734.2		c.1905G>C	p.Arg635Arg	synonymous	Exon 10 of 12	NP_001268663.1	Q9HBF4-3
	ZFYVE1	NM_001281735.1		c.702G>C	p.Arg234Arg	synonymous	Exon 7 of 9	NP_001268664.1	Q9HBF4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE1	ENST00000556143.6	TSL:1 MANE Select	c.1947G>C	p.Arg649Arg	synonymous	Exon 10 of 12	ENSP00000450742.1	Q9HBF4-1
	ZFYVE1	ENST00000318876.9	TSL:1	c.1905G>C	p.Arg635Arg	synonymous	Exon 10 of 12	ENSP00000326921.5	Q9HBF4-3
	ZFYVE1	ENST00000555072.1	TSL:1	c.702G>C	p.Arg234Arg	synonymous	Exon 7 of 9	ENSP00000452232.1	Q9HBF4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.2
DANN	Benign	0.61
PhyloP100		-2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-73441527;