chr4-44624659-C-A

Position:

• chr4-44624659-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_182592.3(YIPF7):​c.550G>T​(p.Gly184Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: YIPF7 NM_182592.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YIPF7	NM_182592.3	c.550G>T	p.Gly184Cys	missense_variant	5/6	ENST00000415895.9	NP_872398.3
YIPF7	XM_047450094.1	c.799G>T	p.Gly267Cys	missense_variant	6/7		XP_047306050.1
YIPF7	XM_011513679.3	c.736G>T	p.Gly246Cys	missense_variant	6/7		XP_011511981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YIPF7	ENST00000415895.9	c.550G>T	p.Gly184Cys	missense_variant	5/6	5	NM_182592.3	ENSP00000412696.4
YIPF7	ENST00000684735.1	c.145-2083G>T		intron_variant				ENSP00000507774.1
YIPF7	ENST00000682193.1	n.*271G>T		non_coding_transcript_exon_variant	3/3			ENSP00000508150.1
YIPF7	ENST00000682193.1	n.*271G>T		3_prime_UTR_variant	3/3			ENSP00000508150.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452300 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 721268

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

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

Nov 16, 2021

The c.622G>T (p.G208C) alteration is located in exon 5 (coding exon 5) of the YIPF7 gene. This alteration results from a G to T substitution at nucleotide position 622, causing the glycine (G) at amino acid position 208 to be replaced by a cysteine (C). 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	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	.;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Pathogenic	3.9	.;H
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-8.1	.;D
REVEL	Pathogenic	0.76
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.97
MutPred		0.89		.;Gain of catalytic residue at G208 (P = 0.0366);
MVP		0.56
MPC		0.057
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.80
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-44626676;