5-144165488-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM1 BP4_Strong BP6_Moderate BS1 BS2

The NM_030799.9(YIPF5):c.227C>T(p.Ala76Val) variant causes a missense change. The variant allele was found at a frequency of 0.021 in 1,614,122 control chromosomes in the GnomAD database, including 413 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (26 hom., cov: 32)
  • Exomes 𝑓: 0.022 (387 hom.)
• Consequence: YIPF5 NM_030799.9 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.80

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 Benign. Variant got -12 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
• BP4: Computational evidence support a benign effect (MetaRNN=0.004816413).
• BP6: Variant 5-144165488-G-A is Benign according to our data. Variant chr5-144165488-G-A is described in ClinVar as [Benign]. Clinvar id is 2655875.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0149 (2264/152276) while in subpopulation NFE AF= 0.0245 (1667/68014). AF 95% confidence interval is 0.0235. There are 26 homozygotes in gnomad4. There are 1000 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YIPF5	NM_030799.9	c.227C>T	p.Ala76Val	missense_variant	3/6	ENST00000274496.10
YIPF5	NM_001024947.4	c.227C>T	p.Ala76Val	missense_variant	3/6
YIPF5	NM_001271732.2	c.65C>T	p.Ala22Val	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIPF5	ENST00000274496.10	c.227C>T	p.Ala76Val	missense_variant	3/6	1	NM_030799.9	P1

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2261 AN: 152158 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.00471

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.00773

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.0141 AC: 3555 AN: 251470 Hom.: 38 AF XY: 0.0146 AC XY: 1981 AN XY: 135906

Gnomad AFR exome AF: 0.00468

Gnomad AMR exome AF: 0.00708

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00657

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.0228

Gnomad OTH exome AF: 0.0163

GnomAD4 exome AF: 0.0217 AC: 31662 AN: 1461846 Hom.: 387 Cov.: 31 AF XY: 0.0212 AC XY: 15431 AN XY: 727226

Gnomad4 AFR exome AF: 0.00424

Gnomad4 AMR exome AF: 0.00751

Gnomad4 ASJ exome AF: 0.0117

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00634

Gnomad4 FIN exome AF: 0.0100

Gnomad4 NFE exome AF: 0.0257

Gnomad4 OTH exome AF: 0.0168

GnomAD4 genome AF: 0.0149 AC: 2264 AN: 152276 Hom.: 26 Cov.: 32 AF XY: 0.0134 AC XY: 1000 AN XY: 74466

Gnomad4 AFR AF: 0.00469

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.00773

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0221 Hom.: 43

Bravo AF: 0.0146

TwinsUK AF: 0.0329 AC: 122

ALSPAC AF: 0.0296 AC: 114

ESP6500AA AF: 0.00477 AC: 21

ESP6500EA AF: 0.0228 AC: 196

ExAC AF: 0.0136 AC: 1656

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0265

EpiControl AF: 0.0232

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

YIPF5: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	17
Dann	Benign	0.97
DEOGEN2	Benign	0.017	T;T;.;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.94	D
MetaRNN	Benign	0.0048	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.68	N;N;N;N;N
REVEL	Benign	0.031
Sift	Benign	0.39	T;T;T;T;T
Sift4G	Benign	0.31	T;T;T;T;.
Polyphen		0.0	B;B;.;.;.
Vest4		0.099
MPC		0.12
ClinPred		0.0084	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.36

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

Other links and lift over

dbSNP: rs35429531; hg19: chr5-143545052; COSMIC: COSV99070204;