15-40814287-A-G

Variant names:

• chr15-40814287-A-G
• rs7915
• NM_001077268.2:c.*61A>G

Variant summary

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

The NM_001077268.2(ZFYVE19):​c.*61A>G variant causes a 3 prime UTR 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: 33)
• Consequence: ZFYVE19 NM_001077268.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 25 publications found

Genes affected

ZFYVE19 (HGNC:20758): (zinc finger FYVE-type containing 19) Enables phosphatidylinositol-3-phosphate binding activity. Involved in abscission; mitotic cytokinesis checkpoint signaling; and negative regulation of cytokinesis. Located in centrosome; cleavage furrow; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ZFYVE19 Gene-Disease associations (from GenCC):

• cholestasis, progressive familial intrahepatic, 9

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

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 (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077268.2. 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
	ZFYVE19	NM_001077268.2	MANE Select	c.*61A>G		3_prime_UTR	Exon 11 of 11	NP_001070736.1
	ZFYVE19	NM_032850.5		c.*61A>G		3_prime_UTR	Exon 12 of 12	NP_116239.3
	ZFYVE19	NM_001258420.2		c.*61A>G		3_prime_UTR	Exon 10 of 10	NP_001245349.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE19	ENST00000355341.8	TSL:1 MANE Select	c.*61A>G		3_prime_UTR	Exon 11 of 11	ENSP00000347498.4
	ZFYVE19	ENST00000299173.14	TSL:1	c.*61A>G		3_prime_UTR	Exon 10 of 10	ENSP00000299173.10
	ZFYVE19	ENST00000560078.1	TSL:2	n.2631A>G		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.71
PhyloP100		-0.17

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: rs7915; hg19: chr15-41106485;