chr2-32292264-A-C

Position:

• chr2-32292264-A-C

Variant summary

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

The NM_032312.4(YIPF4):​c.321A>C​(p.Gln107His) 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: 2.69

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	UniProt
YIPF4	NM_032312.4	c.321A>C	p.Gln107His	missense_variant	3/6	ENST00000238831.9
YIPF4	XM_005264599.4	c.321A>C	p.Gln107His	missense_variant	3/6
YIPF4	XM_024453173.2	c.321A>C	p.Gln107His	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIPF4	ENST00000238831.9	c.321A>C	p.Gln107His	missense_variant	3/6	1	NM_032312.4	P1
YIPF4	ENST00000437765.1	c.158+1628A>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 17, 2021

The c.321A>C (p.Q107H) alteration is located in exon 3 (coding exon 3) of the YIPF4 gene. This alteration results from a A to C substitution at nucleotide position 321, causing the glutamine (Q) at amino acid position 107 to be replaced by a histidine (H). 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	Uncertain	0.42
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.32	N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.21
Sift	Benign	0.16	T
Sift4G	Benign	0.26	T
Polyphen		0.99	D
Vest4		0.76
MutPred		0.61		Gain of methylation at R110 (P = 0.0486);
MVP		0.31
MPC		0.39
ClinPred		0.82	D
GERP RS		4.3
Varity_R		0.11
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr2-32517333;