dbSNP rs1031766879: YIPF1:p.Pro75Arg (chr1-53878694-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018982.5(YIPF1):c.224C>G(p.Pro75Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000877 in 1,597,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

YIPF1
NM_018982.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.70

Publications

0 publications found

Variant links:

Genes affected

YIPF1 (HGNC:25231): (Yip1 domain family member 1) Predicted to enable small GTPase binding activity. Predicted to be involved in vesicle-mediated transport. Located in several cellular components, including Golgi apparatus subcompartment; nucleoplasm; and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

YIPF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018982.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YIPF1	NM_018982.5	MANE Select	c.224C>G	p.Pro75Arg	missense	Exon 5 of 11	NP_061855.1	Q9Y548-1
YIPF1	NR_036639.2		n.578C>G		non_coding_transcript_exon	Exon 5 of 12
YIPF1	NR_036640.2		n.358C>G		non_coding_transcript_exon	Exon 4 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YIPF1	ENST00000072644.7	TSL:1 MANE Select	c.224C>G	p.Pro75Arg	missense	Exon 5 of 11	ENSP00000072644.1	Q9Y548-1
YIPF1	ENST00000464950.6	TSL:1	n.224C>G		non_coding_transcript_exon	Exon 4 of 11	ENSP00000432266.1	Q9Y548-1
YIPF1	ENST00000854787.1		c.224C>G	p.Pro75Arg	missense	Exon 5 of 11	ENSP00000524846.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000431

AC:

AN:

232260

AF XY:

0.00000793

show subpopulations

Gnomad AFR exome

AF:

0.0000633

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000415

AC:

AN:

1444928

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

718994

show subpopulations

African (AFR)

AF:

0.000156

AC:

AN:

32074

American (AMR)

AF:

0.00

AC:

AN:

37570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25360

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.00

AC:

AN:

83136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108450

Other (OTH)

AF:

0.0000167

AC:

AN:

59760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.0000526

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

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:

0.00

Hom.:

Bravo

AF:

0.0000416

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

0.18

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.7

PhyloP100

8.7

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.33

Sift

Benign

0.20

Sift4G

Benign

0.26

Polyphen

1.0

Vest4

0.86

MutPred

0.40

Loss of glycosylation at P75 (P = 0.0258)

MVP

0.095

MPC

0.23

ClinPred

0.51

GERP RS

4.9

Varity_R

0.31

gMVP

0.64

Mutation Taster

=204/96

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