2-32298288-C-A

Position:

• chr2-32298288-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032312.4(YIPF4):​c.460C>A​(p.Leu154Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YIPF4 NM_032312.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YIPF4	NM_032312.4	c.460C>A	p.Leu154Met	missense_variant	4/6	ENST00000238831.9	NP_115688.1
YIPF4	XM_005264599.4	c.460C>A	p.Leu154Met	missense_variant	4/6		XP_005264656.1
YIPF4	XM_024453173.2	c.406-3094C>A		intron_variant			XP_024308941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YIPF4	ENST00000238831.9	c.460C>A	p.Leu154Met	missense_variant	4/6	1	NM_032312.4	ENSP00000238831.3
YIPF4	ENST00000437765.1	n.*36C>A		non_coding_transcript_exon_variant	3/5	5		ENSP00000394339.1
YIPF4	ENST00000437765.1	n.*36C>A		3_prime_UTR_variant	3/5	5		ENSP00000394339.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Jan 04, 2022

The c.460C>A (p.L154M) alteration is located in exon 4 (coding exon 4) of the YIPF4 gene. This alteration results from a C to A substitution at nucleotide position 460, causing the leucine (L) at amino acid position 154 to be replaced by a methionine (M). 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	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.25
Sift	Benign	0.086	T
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.69		Gain of methylation at R156 (P = 0.2589);
MVP		0.19
MPC		0.45
ClinPred		0.95	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-32523357;