Variant 4-44624754-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_182592.3(YIPF7):c.455A>G(p.Tyr152Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,382 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

Variant links:

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]

YIPF7 links:

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ACMG classification

Classification made for transcript

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, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YIPF7	NM_182592.3 link	c.455A>G	p.Tyr152Cys	missense_variant	5/6	ENST00000415895.9	NP_872398.3	Q8N8F6
YIPF7	XM_047450094.1 link	c.704A>G	p.Tyr235Cys	missense_variant	6/7		XP_047306050.1
YIPF7	XM_011513679.3 link	c.641A>G	p.Tyr214Cys	missense_variant	6/7		XP_011511981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
YIPF7	ENST00000415895.9 link	c.455A>G	p.Tyr152Cys	missense_variant	5/6	5	NM_182592.3	ENSP00000412696.4	J3KR00
YIPF7	ENST00000684735.1 link	c.145-2178A>G		intron_variant				ENSP00000507774.1	A0A804HK52
YIPF7	ENST00000682193.1 link	n.*176A>G		non_coding_transcript_exon_variant	3/3			ENSP00000508150.1	A0A804HL09
YIPF7	ENST00000682193.1 link	n.*176A>G		3_prime_UTR_variant	3/3			ENSP00000508150.1	A0A804HL09

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459382

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725638

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.527A>G (p.Y176C) alteration is located in exon 5 (coding exon 5) of the YIPF7 gene. This alteration results from a A to G substitution at nucleotide position 527, causing the tyrosine (Y) at amino acid position 176 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

Benign

0.17

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

.;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.056

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Benign

-0.33

MutationAssessor

Pathogenic

3.4

.;M

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-8.6

.;D

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.96

MutPred

0.92

.;Loss of stability (P = 0.3794);

MVP

0.39

MPC

0.056

ClinPred

1.0

GERP RS

3.9

Varity_R

0.61

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over