11-66284641-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020470.3(YIF1A):​c.878G>A​(p.Arg293Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,612,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

YIF1A
NM_020470.3 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.36
Variant links:
Genes affected
YIF1A (HGNC:16688): (Yip1 interacting factor homolog A, membrane trafficking protein) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Located in Golgi apparatus and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]
CNIH2 (HGNC:28744): (cornichon family AMPA receptor auxiliary protein 2) The protein encoded by this gene is an auxiliary subunit of the ionotropic glutamate receptor of the AMPA subtype. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system. This protein has been reported to interact with the Type I AMPA receptor regulatory protein isoform gamma-8 to control assembly of hippocampal AMPA receptor complexes, thereby modulating receptor gating and pharmacology. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08773661).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
YIF1ANM_020470.3 linkc.878G>A p.Arg293Gln missense_variant Exon 8 of 8 ENST00000376901.9 NP_065203.2 O95070A8K509
YIF1ANM_001300861.2 linkc.722G>A p.Arg241Gln missense_variant Exon 7 of 7 NP_001287790.1 A6NGW1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
YIF1AENST00000376901.9 linkc.878G>A p.Arg293Gln missense_variant Exon 8 of 8 1 NM_020470.3 ENSP00000366098.4 O95070

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152170
Hom.:
0
Cov.:
33
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:
0.000577
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000606
AC:
15
AN:
247702
Hom.:
0
AF XY:
0.0000593
AC XY:
8
AN XY:
134956
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000709
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000899
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1460372
Hom.:
0
Cov.:
31
AF XY:
0.0000275
AC XY:
20
AN XY:
726472
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152170
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000577
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000578
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 23, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.878G>A (p.R293Q) alteration is located in exon 8 (coding exon 8) of the YIF1A gene. This alteration results from a G to A substitution at nucleotide position 878, causing the arginine (R) at amino acid position 293 to be replaced by a glutamine (Q). 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
0.13
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.028
T;T;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.088
T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
1.9
.;.;L
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.15
Sift
Uncertain
0.0050
D;T;T
Sift4G
Pathogenic
0.0
D;T;T
Polyphen
0.98
.;.;D
Vest4
0.30
MVP
0.50
MPC
0.28
ClinPred
0.31
T
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.28
gMVP
0.80

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.

Other links and lift over

dbSNP: rs1455781753; hg19: chr11-66052112; API