4-44635988-T-C

Position:

• chr4-44635988-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.214A>G​(p.Asn72Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 2.32

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=0.16906884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YIPF7	NM_182592.3	c.214A>G	p.Asn72Asp	missense_variant	3/6	ENST00000415895.9	NP_872398.3
YIPF7	NM_001387382.1	c.214A>G	p.Asn72Asp	missense_variant	3/3		NP_001374311.1
YIPF7	XM_047450094.1	c.463A>G	p.Asn155Asp	missense_variant	4/7		XP_047306050.1
YIPF7	XM_011513679.3	c.400A>G	p.Asn134Asp	missense_variant	4/7		XP_011511981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YIPF7	ENST00000415895.9	c.214A>G	p.Asn72Asp	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

Oct 09, 2024

The c.286A>G (p.N96D) 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 286, causing the asparagine (N) at amino acid position 96 to be replaced by an aspartic acid (D). 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	0.072
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.015	.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	.;N
REVEL	Benign	0.098
Sift	Benign	0.37	.;T
Sift4G	Benign	0.37	T;T
Polyphen		0.0	.;B
Vest4		0.16
MutPred		0.17		.;Gain of glycosylation at Y99 (P = 0.0061);
MVP		0.055
MPC		0.0090
ClinPred		0.45	T
GERP RS		5.0
Varity_R		0.13
gMVP		0.28

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: rs1713105037; hg19: chr4-44638005;