Variant 5-144160557-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_030799.9(YIPF5):c.614G>A(p.Gly205Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

YIPF5
NM_030799.9 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.82

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.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
YIPF5	NM_030799.9 linkuse as main transcript	c.614G>A	p.Gly205Glu	missense_variant, splice_region_variant	6/6	ENST00000274496.10	NP_110426.4
YIPF5	NM_001024947.4 linkuse as main transcript	c.614G>A	p.Gly205Glu	missense_variant, splice_region_variant	6/6		NP_001020118.1
YIPF5	NM_001271732.2 linkuse as main transcript	c.452G>A	p.Gly151Glu	missense_variant, splice_region_variant	5/5		NP_001258661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YIPF5	ENST00000274496.10 linkuse as main transcript	c.614G>A	p.Gly205Glu	missense_variant, splice_region_variant	6/6	1	NM_030799.9	ENSP00000274496	P1	Q969M3-1
YIPF5	ENST00000448443.6 linkuse as main transcript	c.614G>A	p.Gly205Glu	missense_variant, splice_region_variant	6/6	1		ENSP00000397704	P1	Q969M3-1
YIPF5	ENST00000513112.5 linkuse as main transcript	c.452G>A	p.Gly151Glu	missense_variant, splice_region_variant	5/5	1		ENSP00000425422		Q969M3-2
YIPF5	ENST00000519064.5 linkuse as main transcript	c.452G>A	p.Gly151Glu	missense_variant, splice_region_variant	5/5	2		ENSP00000429777

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245368

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132884

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:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457348

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724750

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 24, 2024

The c.614G>A (p.G205E) alteration is located in exon 6 (coding exon 5) of the YIPF5 gene. This alteration results from a G to A substitution at nucleotide position 614, causing the glycine (G) at amino acid position 205 to be replaced by a glutamic acid (E). 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

0.83

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;.;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

.;D;D;D

M_CAP

Benign

0.027

MetaRNN

Pathogenic

0.87

D;D;D;D

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

3.6

H;H;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-6.0

D;D;D;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.99

D;D;.;.

Vest4

0.87

MutPred

0.69

Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;.;

MVP

0.55

MPC

0.33

ClinPred

0.98

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.91

gMVP

0.87

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