Genetic Variant YIF1A:p.Asp257Asn (chr11-66284750-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020470.3(YIF1A):c.769G>A(p.Asp257Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,611,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

YIF1A
NM_020470.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.485

Publications

1 publications found

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]

YIF1A links:

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]

CNIH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055803508).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020470.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YIF1A	NM_020470.3	MANE Select	c.769G>A	p.Asp257Asn	missense	Exon 8 of 8	NP_065203.2	O95070
	YIF1A	NM_001300861.2		c.613G>A	p.Asp205Asn	missense	Exon 7 of 7	NP_001287790.1	A6NGW1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YIF1A	ENST00000376901.9	TSL:1 MANE Select	c.769G>A	p.Asp257Asn	missense	Exon 8 of 8	ENSP00000366098.4	O95070
YIF1A	ENST00000715691.1		c.769G>A	p.Asp257Asn	missense	Exon 8 of 8	ENSP00000520502.1	O95070
YIF1A	ENST00000359461.10	TSL:2	c.613G>A	p.Asp205Asn	missense	Exon 7 of 7	ENSP00000352437.6	A6NGW1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

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:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000487

AC:

AN:

246514

AF XY:

0.0000298

show subpopulations

Gnomad AFR exome

AF:

0.000518

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000137

AC:

AN:

1459760

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726138

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33450

American (AMR)

AF:

0.0000448

AC:

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111636

Other (OTH)

AF:

0.0000166

AC:

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41540

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000413

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.029

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

PhyloP100

0.48

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

REVEL

Benign

0.090

Sift

Benign

0.47

Sift4G

Benign

0.23

Polyphen

0.17

Vest4

0.33

MVP

0.60

MPC

0.098

ClinPred

0.069

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.67

Mutation Taster

=77/23

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over