5-80481068-G-C

Variant names:

• chr5-80481068-G-C
• rs701380
• NM_001284236.3:c.*3691G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001284236.3(ZFYVE16):​c.*3691G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,072 control chromosomes in the GnomAD database, including 48,883 homozygotes. 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: 𝑓 0.78 (48883 hom., cov: 30)
• Consequence: ZFYVE16 NM_001284236.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE16	NM_001284236.3	c.*3691G>C		3_prime_UTR_variant	Exon 19 of 19	ENST00000505560.5	NP_001271165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE16	ENST00000505560.5	c.*3691G>C		3_prime_UTR_variant	Exon 19 of 19	1	NM_001284236.3	ENSP00000426848.1
FAM151B-DT	ENST00000504300.3	n.2519C>G		non_coding_transcript_exon_variant	Exon 3 of 3	2
FAM151B-DT	ENST00000508000.6	n.2493C>G		non_coding_transcript_exon_variant	Exon 3 of 3	2
FAM151B-DT	ENST00000666568.1	n.258+4398C>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117956 AN: 151956 Hom.: 48884 Cov.: 30

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.776 AC: 117977 AN: 152072 Hom.: 48883 Cov.: 30 AF XY: 0.778 AC XY: 57860 AN XY: 74348

African (AFR) AF: 0.450 AC: 18626 AN: 41428

American (AMR) AF: 0.872 AC: 13322 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3188 AN: 3472

East Asian (EAS) AF: 0.919 AC: 4748 AN: 5168

South Asian (SAS) AF: 0.802 AC: 3850 AN: 4802

European-Finnish (FIN) AF: 0.909 AC: 9648 AN: 10610

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.909 AC: 61819 AN: 68008

Other (OTH) AF: 0.794 AC: 1673 AN: 2108

Alfa AF: 0.800 Hom.: 3244

Bravo AF: 0.759

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.72
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs701380; hg19: chr5-79776887; COSMIC: COSV62015098;