5-144160405-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM1BP4_StrongBP6_ModerateBS2

The NM_030799.9(YIPF5):c.766G>A(p.Val256Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00896 in 1,611,456 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 92 hom. )

Consequence

YIPF5
NM_030799.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 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

BP4

Computational evidence support a benign effect (MetaRNN=0.0073158443).

BP6

Variant 5-144160405-C-T is Benign according to our data. Variant chr5-144160405-C-T is described in ClinVar as [Benign]. Clinvar id is 2655874.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
YIPF5	NM_030799.9 linkuse as main transcript	c.766G>A	p.Val256Ile	missense_variant	6/6	ENST00000274496.10
YIPF5	NM_001024947.4 linkuse as main transcript	c.766G>A	p.Val256Ile	missense_variant	6/6
YIPF5	NM_001271732.2 linkuse as main transcript	c.604G>A	p.Val202Ile	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIPF5	ENST00000274496.10 linkuse as main transcript	c.766G>A	p.Val256Ile	missense_variant	6/6	1	NM_030799.9	P1	Q969M3-1
YIPF5	ENST00000448443.6 linkuse as main transcript	c.766G>A	p.Val256Ile	missense_variant	6/6	1		P1	Q969M3-1
YIPF5	ENST00000513112.5 linkuse as main transcript	c.604G>A	p.Val202Ile	missense_variant	5/5	1			Q969M3-2

Frequencies

GnomAD3 genomes

AF:

0.00592

AC:

900

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00588

AC:

1472

AN:

250324

Hom.:

AF XY:

0.00602

AC XY:

815

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00312

Gnomad ASJ exome

AF:

0.00868

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00145

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00786

GnomAD4 exome

AF:

0.00928

AC:

13543

AN:

1459236

Hom.:

Cov.:

AF XY:

0.00912

AC XY:

6618

AN XY:

725680

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.00330

Gnomad4 ASJ exome

AF:

0.00840

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00176

Gnomad4 FIN exome

AF:

0.00146

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00854

GnomAD4 genome

AF:

0.00591

AC:

900

AN:

152220

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

420

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00871

Hom.:

Bravo

AF:

0.00597

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.0113

AC:

ExAC

AF:

0.00587

AC:

713

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

YIPF5: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

Cadd

Benign

Dann

Benign

0.66

DEOGEN2

Benign

0.0050

T;T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.60

MetaRNN

Benign

0.0073

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.17

N;N;N

REVEL

Benign

0.076

Sift

Benign

0.73

T;T;T

Sift4G

Benign

0.65

T;T;T

Polyphen

0.51

P;P;.

Vest4

0.070

MVP

0.043

MPC

0.094

ClinPred

0.0049

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.014

gMVP

0.43

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

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