Variant chr4-44629508-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182592.3(YIPF7):c.321G>T(p.Leu107Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000433 in 1,572,094 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

YIPF7
NM_182592.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 link	c.321G>T	p.Leu107Phe	missense_variant	4/6	ENST00000415895.9	NP_872398.3	Q8N8F6
YIPF7	XM_047450094.1 link	c.570G>T	p.Leu190Phe	missense_variant	5/7		XP_047306050.1
YIPF7	XM_011513679.3 link	c.507G>T	p.Leu169Phe	missense_variant	5/7		XP_011511981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YIPF7	ENST00000415895.9 link	c.321G>T	p.Leu107Phe	missense_variant	4/6	5	NM_182592.3	ENSP00000412696.4		J3KR00

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000362

AC:

AN:

193612

Hom.:

AF XY:

0.0000386

AC XY:

AN XY:

103636

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000813

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000478

Gnomad OTH exome

AF:

0.000201

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1420026

Hom.:

Cov.:

AF XY:

0.0000526

AC XY:

AN XY:

703410

show subpopulations

Gnomad4 AFR exome

AF:

0.000494

Gnomad4 AMR exome

AF:

0.0000256

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000375

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000330

Gnomad4 OTH exome

AF:

0.000119

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00000832

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Aug 16, 2022

The c.393G>T (p.L131F) alteration is located in exon 4 (coding exon 4) of the YIPF7 gene. This alteration results from a G to T substitution at nucleotide position 393, causing the leucine (L) at amino acid position 131 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

Benign

0.16

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.6

.;M

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.0

.;D

REVEL

Benign

0.20

Sift

Benign

0.062

.;T

Sift4G

Benign

0.099

T;T

Polyphen

0.75

.;P

Vest4

0.59

MutPred

0.63

.;Gain of ubiquitination at K129 (P = 0.0846);

MVP

0.19

MPC

0.050

ClinPred

0.77

GERP RS

4.4

Varity_R

0.15

gMVP

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over