2-32305501-T-C

Position:

• chr2-32305501-T-C

Variant summary

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

The NM_032312.4(YIPF4):​c.610T>C​(p.Phe204Leu) variant causes a missense change involving the alteration of a 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: 7.65

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.610T>C	p.Phe204Leu	missense_variant	6/6	ENST00000238831.9	NP_115688.1
YIPF4	XM_005264599.4	c.598-1603T>C		intron_variant			XP_005264656.1
YIPF4	XM_024453173.2	c.520-1603T>C		intron_variant			XP_024308941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YIPF4	ENST00000238831.9	c.610T>C	p.Phe204Leu	missense_variant	6/6	1	NM_032312.4	ENSP00000238831.3
YIPF4	ENST00000441084.1	c.52-1603T>C		intron_variant		3		ENSP00000414267.1
YIPF4	ENST00000437765.1	n.*186T>C		non_coding_transcript_exon_variant	5/5	5		ENSP00000394339.1
YIPF4	ENST00000437765.1	n.*186T>C		3_prime_UTR_variant	5/5	5		ENSP00000394339.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 27, 2022

The c.610T>C (p.F204L) alteration is located in exon 6 (coding exon 6) of the YIPF4 gene. This alteration results from a T to C substitution at nucleotide position 610, causing the phenylalanine (F) at amino acid position 204 to be replaced by a leucine (L). 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	0.71
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.29	N
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.24
Sift	Benign	0.53	T
Sift4G	Benign	0.86	T
Polyphen		0.39	B
Vest4		0.79
MutPred		0.50		Loss of catalytic residue at F204 (P = 0.0864);
MVP		0.13
MPC		0.10
ClinPred		0.79	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.78

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: chr2-32530570;