Genetic Variant APIP:p.Arg67Gln (chr11-34890511-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015957.4(APIP):c.200G>A(p.Arg67Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000715 in 1,609,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

APIP
NM_015957.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04

Publications

2 publications found

Variant links:

Genes affected

APIP (HGNC:17581): (APAF1 interacting protein) Enables identical protein binding activity; methylthioribulose 1-phosphate dehydratase activity; and zinc ion binding activity. Involved in several processes, including L-methionine salvage from methylthioadenosine; protein homotetramerization; and pyroptosis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

APIP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0787735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015957.4. 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
	APIP	NM_015957.4	MANE Select	c.200G>A	p.Arg67Gln	missense	Exon 3 of 7	NP_057041.2	Q96GX9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APIP	ENST00000395787.4	TSL:1 MANE Select	c.200G>A	p.Arg67Gln	missense	Exon 3 of 7	ENSP00000379133.3	Q96GX9-1
APIP	ENST00000532428.6	TSL:1	n.59G>A		non_coding_transcript_exon	Exon 1 of 8	ENSP00000474191.1	S4R3D6
APIP	ENST00000901543.1		c.200G>A	p.Arg67Gln	missense	Exon 3 of 8	ENSP00000571602.1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000145

AC:

AN:

248968

AF XY:

0.000111

show subpopulations

Gnomad AFR exome

AF:

0.000806

Gnomad AMR exome

AF:

0.000326

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000219

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.0000556

AC:

AN:

1457064

Hom.:

Cov.:

AF XY:

0.0000524

AC XY:

AN XY:

724854

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33280

American (AMR)

AF:

0.000384

AC:

AN:

44300

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26020

East Asian (EAS)

AF:

0.000101

AC:

AN:

39490

South Asian (SAS)

AF:

0.000199

AC:

AN:

85584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5330

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1109710

Other (OTH)

AF:

0.0000665

AC:

AN:

60154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.000223

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41564

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67978

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000555

Hom.:

Bravo

AF:

0.000283

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

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

Uncertain

0.41

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.026

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.97

MutationAssessor

Benign

2.0

PhyloP100

5.0

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.15

Sift

Benign

0.099

Sift4G

Benign

0.084

Polyphen

0.019

Vest4

0.60

MVP

0.34

MPC

0.40

ClinPred

0.036

GERP RS

5.5

Varity_R

0.79

gMVP

0.66

Mutation Taster

=7/93

disease causing

(source)

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

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