15-40807371-C-G

Position:

chr15-40807371-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001077268.2(ZFYVE19):c.-219C>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000805 in 1,614,162 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ZFYVE19
NM_001077268.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

Variant links:

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 links:

DNAJC17 (HGNC:25556): (DnaJ heat shock protein family (Hsp40) member C17) Predicted to enable RNA binding activity. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II and toxin transport. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC17 links:

DNAJC17 (HGNC:):

DNAJC17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE19	NM_001077268.2 linkuse as main transcript	c.-219C>G		5_prime_UTR_premature_start_codon_gain_variant	1/11	ENST00000355341.8	NP_001070736.1	Q96K21-1
DNAJC17	NM_018163.3 linkuse as main transcript	c.76G>C	p.Glu26Gln	missense_variant, splice_region_variant	1/11	ENST00000220496.9	NP_060633.1	Q9NVM6
ZFYVE19	NM_001077268.2 linkuse as main transcript	c.-219C>G		5_prime_UTR_variant	1/11	ENST00000355341.8	NP_001070736.1	Q96K21-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZFYVE19	ENST00000355341 linkuse as main transcript	c.-219C>G		5_prime_UTR_premature_start_codon_gain_variant	1/11	1	NM_001077268.2	ENSP00000347498.4	Q96K21-1
DNAJC17	ENST00000220496.9 linkuse as main transcript	c.76G>C	p.Glu26Gln	missense_variant, splice_region_variant	1/11	1	NM_018163.3	ENSP00000220496.4	Q9NVM6
ZFYVE19	ENST00000355341 linkuse as main transcript	c.-219C>G		5_prime_UTR_variant	1/11	1	NM_001077268.2	ENSP00000347498.4	Q96K21-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.76G>C (p.E26Q) alteration is located in exon 1 (coding exon 1) of the DNAJC17 gene. This alteration results from a G to C substitution at nucleotide position 76, causing the glutamic acid (E) at amino acid position 26 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;.

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.20

Sift

Benign

0.11

T;.

Sift4G

Benign

0.17

T;T

Polyphen

0.25

B;.

Vest4

0.70

MutPred

0.75

Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);

MVP

0.45

MPC

0.34

ClinPred

0.88

GERP RS

5.3

Varity_R

0.44

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over