Variant 5-144162293-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_030799.9(YIPF5):c.536G>T(p.Cys179Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000458 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

YIPF5
NM_030799.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

Variant links:

Genes affected

YIPF5 (HGNC:24877): (Yip1 domain family member 5) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport; regulation of ER to Golgi vesicle-mediated transport; and vesicle fusion with Golgi apparatus. Located in Golgi apparatus; endoplasmic reticulum; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

YIPF5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a chain Protein YIPF5 (size 256) in uniprot entity YIPF5_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in NM_030799.9

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
YIPF5	NM_030799.9 linkuse as main transcript	c.536G>T	p.Cys179Phe	missense_variant	5/6	ENST00000274496.10
YIPF5	NM_001024947.4 linkuse as main transcript	c.536G>T	p.Cys179Phe	missense_variant	5/6
YIPF5	NM_001271732.2 linkuse as main transcript	c.374G>T	p.Cys125Phe	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIPF5	ENST00000274496.10 linkuse as main transcript	c.536G>T	p.Cys179Phe	missense_variant	5/6	1	NM_030799.9	P1	Q969M3-1
YIPF5	ENST00000448443.6 linkuse as main transcript	c.536G>T	p.Cys179Phe	missense_variant	5/6	1		P1	Q969M3-1
YIPF5	ENST00000513112.5 linkuse as main transcript	c.374G>T	p.Cys125Phe	missense_variant	4/5	1			Q969M3-2
YIPF5	ENST00000519064.5 linkuse as main transcript	c.374G>T	p.Cys125Phe	missense_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251416

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461818

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000567

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Mar 01, 2023

The c.536G>T (p.C179F) alteration is located in exon 5 (coding exon 4) of the YIPF5 gene. This alteration results from a G to T substitution at nucleotide position 536, causing the cysteine (C) at amino acid position 179 to be replaced by a phenylalanine (F). 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

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.091

BayesDel_noAF

Uncertain

0.090

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.086

T;T;.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.53

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-6.4

D;D;D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.020

D;D;T;T

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.27

B;B;.;.

Vest4

0.85

MutPred

0.47

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);.;.;

MVP

0.64

MPC

0.27

ClinPred

0.48

GERP RS

5.7

Varity_R

0.76

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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