Variant chr4-44624704-T-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.505A>T(p.Met169Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

YIPF7
NM_182592.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.94

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 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.505A>T	p.Met169Leu	missense_variant	5/6	ENST00000415895.9	NP_872398.3	Q8N8F6
YIPF7	XM_047450094.1 link	c.754A>T	p.Met252Leu	missense_variant	6/7		XP_047306050.1
YIPF7	XM_011513679.3 link	c.691A>T	p.Met231Leu	missense_variant	6/7		XP_011511981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
YIPF7	ENST00000415895.9 link	c.505A>T	p.Met169Leu	missense_variant	5/6	5	NM_182592.3	ENSP00000412696.4	J3KR00
YIPF7	ENST00000684735.1 link	c.145-2128A>T		intron_variant				ENSP00000507774.1	A0A804HK52
YIPF7	ENST00000682193.1 link	n.*226A>T		non_coding_transcript_exon_variant	3/3			ENSP00000508150.1	A0A804HL09
YIPF7	ENST00000682193.1 link	n.*226A>T		3_prime_UTR_variant	3/3			ENSP00000508150.1	A0A804HL09

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000822

AC:

AN:

243184

Hom.:

AF XY:

0.00000760

AC XY:

AN XY:

131592

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458530

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725024

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

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

Dec 22, 2023

The c.577A>T (p.M193L) alteration is located in exon 5 (coding exon 5) of the YIPF7 gene. This alteration results from a A to T substitution at nucleotide position 577, causing the methionine (M) at amino acid position 193 to be replaced by a leucine (L). 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

0.20

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.23

.;T

Eigen

Benign

0.063

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0098

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.5

.;D

REVEL

Benign

0.21

Sift

Benign

0.046

.;D

Sift4G

Uncertain

0.048

D;T

Polyphen

0.23

.;B

Vest4

0.71

MutPred

0.71

.;Loss of glycosylation at S196 (P = 0.0236);

MVP

0.067

MPC

0.011

ClinPred

0.44

GERP RS

5.0

Varity_R

0.32

gMVP

0.54

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

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