Variant 2-32278183-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032312.4(YIPF4):c.28T>G(p.Tyr10Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,421,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

YIPF4
NM_032312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72

Variant links:

Genes affected

YIPF4 (HGNC:28145): (Yip1 domain family member 4) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport and vesicle fusion with Golgi apparatus. Located in Golgi apparatus; endoplasmic reticulum; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

YIPF4 links:

YIPF4 (HGNC:):

YIPF4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16190422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YIPF4	NM_032312.4 linkuse as main transcript	c.28T>G	p.Tyr10Asp	missense_variant	1/6	ENST00000238831.9	NP_115688.1	Q9BSR8
YIPF4	XM_005264599.4 linkuse as main transcript	c.28T>G	p.Tyr10Asp	missense_variant	1/6		XP_005264656.1
YIPF4	XM_024453173.2 linkuse as main transcript	c.28T>G	p.Tyr10Asp	missense_variant	1/5		XP_024308941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
YIPF4	ENST00000238831.9 linkuse as main transcript	c.28T>G	p.Tyr10Asp	missense_variant	1/6	1	NM_032312.4	ENSP00000238831.3	Q9BSR8
YIPF4	ENST00000495355.1 linkuse as main transcript	n.55T>G		non_coding_transcript_exon_variant	1/2	2
YIPF4	ENST00000437765.1 linkuse as main transcript	n.-48T>G		upstream_gene_variant		5		ENSP00000394339.1	H7C0D5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1421050

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703488

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000253

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:

9.16e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000169

AC:

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

May 15, 2024

The c.28T>G (p.Y10D) alteration is located in exon 1 (coding exon 1) of the YIPF4 gene. This alteration results from a T to G substitution at nucleotide position 28, causing the tyrosine (Y) at amino acid position 10 to be replaced by an aspartic acid (D). 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

Benign

0.21

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.020

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.60

M_CAP

Benign

0.015

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.3

REVEL

Benign

0.11

Sift

Benign

0.11

Sift4G

Benign

0.22

Polyphen

0.59

Vest4

0.42

MutPred

0.28

Loss of catalytic residue at Y10 (P = 0.0018);

MVP

0.21

MPC

0.32

ClinPred

0.46

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.49

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