chr4-44636071-T-C

Position:

• chr4-44636071-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182592.3(YIPF7):​c.131A>G​(p.Glu44Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: YIPF7 NM_182592.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

Genes affected

YIPF7 (HGNC:26825): (Yip1 domain family member 7) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport and vesicle fusion with Golgi apparatus. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in trans-Golgi network. [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=0.15533677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YIPF7	NM_182592.3	c.131A>G	p.Glu44Gly	missense_variant	3/6	ENST00000415895.9	NP_872398.3
YIPF7	NM_001387382.1	c.131A>G	p.Glu44Gly	missense_variant	3/3		NP_001374311.1
YIPF7	XM_047450094.1	c.380A>G	p.Glu127Gly	missense_variant	4/7		XP_047306050.1
YIPF7	XM_011513679.3	c.317A>G	p.Glu106Gly	missense_variant	4/7		XP_011511981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YIPF7	ENST00000415895.9	c.131A>G	p.Glu44Gly	missense_variant	3/6	5	NM_182592.3	ENSP00000412696.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Nov 28, 2024

The c.203A>G (p.E68G) alteration is located in exon 3 (coding exon 3) of the YIPF7 gene. This alteration results from a A to G substitution at nucleotide position 203, causing the glutamic acid (E) at amino acid position 68 to be replaced by a glycine (G). 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	0.070
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.0062	.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.73	.;N
REVEL	Benign	0.078
Sift	Benign	0.18	.;T
Sift4G	Benign	0.34	T;T
Polyphen		0.0	.;B
Vest4		0.17
MutPred		0.19		.;Loss of glycosylation at P72 (P = 0.0331);
MVP		0.21
MPC		0.0090
ClinPred		0.13	T
GERP RS		2.2
Varity_R		0.045
gMVP		0.27

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: chr4-44638088; COSMIC: COSV100274604;