4-44622553-G-A

Position:

• chr4-44622553-G-A

Variant summary

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

The NM_182592.3(YIPF7):​c.632C>T​(p.Ser211Phe) 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: YIPF7 NM_182592.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.97

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 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
YIPF7	NM_182592.3	c.632C>T	p.Ser211Phe	missense_variant	6/6	ENST00000415895.9	NP_872398.3
YIPF7	XM_047450094.1	c.881C>T	p.Ser294Phe	missense_variant	7/7		XP_047306050.1
YIPF7	XM_011513679.3	c.818C>T	p.Ser273Phe	missense_variant	7/7		XP_011511981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YIPF7	ENST00000415895.9	c.632C>T	p.Ser211Phe	missense_variant	6/6	5	NM_182592.3	ENSP00000412696.4
YIPF7	ENST00000684735.1	c.168C>T	p.Ile56Ile	synonymous_variant	2/2			ENSP00000507774.1

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

May 07, 2024

The c.704C>T (p.S235F) alteration is located in exon 6 (coding exon 6) of the YIPF7 gene. This alteration results from a C to T substitution at nucleotide position 704, causing the serine (S) at amino acid position 235 to be replaced by a phenylalanine (F). 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	0.44
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.050	N;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.84	.;P
Vest4		0.24
MutPred		0.58		.;Gain of catalytic residue at S235 (P = 0.2184);
MVP		0.41
MPC		0.031
ClinPred		0.94	D
GERP RS		5.2
Varity_R		0.38
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-44624570; COSMIC: COSV60658326;