chr15-40814287-A-C

Variant names:

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

Variant summary

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

The NM_001077268.2(ZFYVE19):​c.*61A>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 0.363 in 1,592,262 control chromosomes in the GnomAD database, including 109,893 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 0.31 (8241 hom., cov: 33)
  • Exomes 𝑓: 0.37 (101652 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

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>C		3_prime_UTR	Exon 11 of 11	NP_001070736.1
	ZFYVE19	NM_032850.5		c.*61A>C		3_prime_UTR	Exon 12 of 12	NP_116239.3
	ZFYVE19	NM_001258420.2		c.*61A>C		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>C		3_prime_UTR	Exon 11 of 11	ENSP00000347498.4
	ZFYVE19	ENST00000299173.14	TSL:1	c.*61A>C		3_prime_UTR	Exon 10 of 10	ENSP00000299173.10
	ZFYVE19	ENST00000560078.1	TSL:2	n.2631A>C		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46598 AN: 152078 Hom.: 8236 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.369 AC: 532084 AN: 1440066 Hom.: 101652 Cov.: 28 AF XY: 0.370 AC XY: 264909 AN XY: 716476

African (AFR) AF: 0.127 AC: 4179 AN: 32954

American (AMR) AF: 0.315 AC: 13505 AN: 42870

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 10089 AN: 25898

East Asian (EAS) AF: 0.675 AC: 26357 AN: 39072

South Asian (SAS) AF: 0.332 AC: 28304 AN: 85156

European-Finnish (FIN) AF: 0.330 AC: 16524 AN: 50080

Middle Eastern (MID) AF: 0.370 AC: 1911 AN: 5160

European-Non Finnish (NFE) AF: 0.373 AC: 409502 AN: 1099244

Other (OTH) AF: 0.364 AC: 21713 AN: 59632

GnomAD4 genome AF: 0.306 AC: 46600 AN: 152196 Hom.: 8241 Cov.: 33 AF XY: 0.309 AC XY: 22986 AN XY: 74396

African (AFR) AF: 0.137 AC: 5689 AN: 41550

American (AMR) AF: 0.330 AC: 5042 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1382 AN: 3470

East Asian (EAS) AF: 0.652 AC: 3372 AN: 5168

South Asian (SAS) AF: 0.345 AC: 1664 AN: 4820

European-Finnish (FIN) AF: 0.331 AC: 3505 AN: 10592

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24761 AN: 67990

Other (OTH) AF: 0.351 AC: 741 AN: 2112

Alfa AF: 0.354 Hom.: 42703

Bravo AF: 0.304

Asia WGS AF: 0.441 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.72
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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;