1-52333341-G-C

Position:

• chr1-52333341-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004799.4(ZFYVE9):​c.3589+423G>C variant causes a intron 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: 27)
• Consequence: ZFYVE9 NM_004799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

Genes affected

ZFYVE9 (HGNC:6775): (zinc finger FYVE-type containing 9) This gene encodes a double zinc finger motif-containing protein that participates in the transforming growth factor-beta (TGFB) signalling pathway. The encoded protein interacts directly with SMAD2 and SMAD3, and recruits SMAD2 to the TGFB receptor. There are multiple pseudogenes for this gene on chromosomes 2, 15, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ZFYVE9 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE9	NM_004799.4	c.3589+423G>C		intron_variant		ENST00000287727.8	NP_004790.2
ZFYVE9	NM_007324.5	c.3412+423G>C		intron_variant			NP_015563.2
ZFYVE9	XM_011542437.3	c.3589+423G>C		intron_variant			XP_011540739.1
ZFYVE9	XM_047434674.1	c.3412+423G>C		intron_variant			XP_047290630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE9	ENST00000287727.8	c.3589+423G>C		intron_variant		5	NM_004799.4	ENSP00000287727.3
ZFYVE9	ENST00000371591.2	c.3589+423G>C		intron_variant		1		ENSP00000360647.1
ZFYVE9	ENST00000357206.6	c.3412+423G>C		intron_variant		1		ENSP00000349737.2
ZFYVE9	ENST00000469134.1	n.339+423G>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 27

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs2762818; hg19: chr1-52799013;