5-144164250-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PP3_Moderate PP5

The NM_030799.9(YIPF5):c.290G>T(p.Gly97Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: YIPF5 NM_030799.9 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.88

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 Likely_pathogenic. Variant got 7 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, 0.919
• PP5: Variant 5-144164250-C-A is Pathogenic according to our data. Variant chr5-144164250-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 1064546.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YIPF5	NM_030799.9	c.290G>T	p.Gly97Val	missense_variant	4/6	ENST00000274496.10
YIPF5	NM_001024947.4	c.290G>T	p.Gly97Val	missense_variant	4/6
YIPF5	NM_001271732.2	c.128G>T	p.Gly43Val	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIPF5	ENST00000274496.10	c.290G>T	p.Gly97Val	missense_variant	4/6	1	NM_030799.9	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453198 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722424

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: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Microcephaly, epilepsy, and diabetes syndrome 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
Cadd	Pathogenic	30
Dann	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T;.;T;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.92	D;D;D;D;D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Pathogenic	4.0	H;H;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-8.6	D;D;D;D;D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;.
Polyphen		1.0	D;D;.;.;.
Vest4		0.90
MutPred		0.77		Loss of disorder (P = 0.075);Loss of disorder (P = 0.075);.;.;.;
MVP		0.78
MPC		0.62
ClinPred		1.0	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.89
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-143543814;