5-144164212-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_030799.9(YIPF5):c.328G>A(p.Val110Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YIPF5 NM_030799.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a topological_domain Cytoplasmic (size 123) in uniprot entity YIPF5_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_030799.9
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.805

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YIPF5	NM_030799.9	c.328G>A	p.Val110Ile	missense_variant	4/6	ENST00000274496.10
YIPF5	NM_001024947.4	c.328G>A	p.Val110Ile	missense_variant	4/6
YIPF5	NM_001271732.2	c.166G>A	p.Val56Ile	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIPF5	ENST00000274496.10	c.328G>A	p.Val110Ile	missense_variant	4/6	1	NM_030799.9	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.328G>A (p.V110I) alteration is located in exon 4 (coding exon 3) of the YIPF5 gene. This alteration results from a G to A substitution at nucleotide position 328, causing the valine (V) at amino acid position 110 to be replaced by an isoleucine (I). 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	Uncertain	0.53
BayesDel_addAF	Benign	0.0088	T
BayesDel_noAF	Benign	-0.23
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T;.;T;.
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.0093	T
MetaRNN	Pathogenic	0.81	D;D;D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.8	M;M;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.96	N;N;N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;.
Polyphen		0.97	D;D;.;.;.
Vest4		0.70
MutPred		0.78		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;.;.;
MVP		0.46
MPC		0.32
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.43
gMVP		0.80

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

Other links and lift over

dbSNP: rs936879035; hg19: chr5-143543776;