2-32278183-T-G

Position:

• chr2-32278183-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.72

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 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	UniProt
YIPF4	NM_032312.4	c.28T>G	p.Tyr10Asp	missense_variant	1/6	ENST00000238831.9
YIPF4	XM_005264599.4	c.28T>G	p.Tyr10Asp	missense_variant	1/6
YIPF4	XM_024453173.2	c.28T>G	p.Tyr10Asp	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIPF4	ENST00000238831.9	c.28T>G	p.Tyr10Asp	missense_variant	1/6	1	NM_032312.4	P1
YIPF4	ENST00000495355.1	n.55T>G		non_coding_transcript_exon_variant	1/2	2
YIPF4	ENST00000437765.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1421050 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 703488

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.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000169 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.11
Sift	Benign	0.11	T
Sift4G	Benign	0.22	T
Polyphen		0.59	P
Vest4		0.42
MutPred		0.28		Loss of catalytic residue at Y10 (P = 0.0018);
MVP		0.21
MPC		0.32
ClinPred		0.46	T
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

Other links and lift over

dbSNP: rs777129844; hg19: chr2-32503252;