dbSNP rs550069903: AFAP1L1:p.Glu174Lys (chr5-149306389-G-A) – 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_152406.4(AFAP1L1):c.520G>A(p.Glu174Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,611,466 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

AFAP1L1
NM_152406.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

Publications

0 publications found

Variant links:

Genes affected

AFAP1L1 (HGNC:26714): (actin filament associated protein 1 like 1) Predicted to enable SH3 domain binding activity. Predicted to be located in cell junction; cell projection; and podosome. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

AFAP1L1 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_152406.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AFAP1L1	NM_152406.4	MANE Select	c.520G>A	p.Glu174Lys	missense	Exon 6 of 19	NP_689619.1	Q8TED9-1
AFAP1L1	NM_001146337.3		c.520G>A	p.Glu174Lys	missense	Exon 6 of 18	NP_001139809.1	Q8TED9-2
AFAP1L1	NM_001323063.2		c.520G>A	p.Glu174Lys	missense	Exon 6 of 9	NP_001309992.1	Q8TED9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AFAP1L1	ENST00000296721.9	TSL:1 MANE Select	c.520G>A	p.Glu174Lys	missense	Exon 6 of 19	ENSP00000296721.4	Q8TED9-1
AFAP1L1	ENST00000515000.1	TSL:1	c.520G>A	p.Glu174Lys	missense	Exon 6 of 18	ENSP00000424427.1	Q8TED9-2
AFAP1L1	ENST00000455574.6	TSL:1	n.618G>A		non_coding_transcript_exon	Exon 6 of 9

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152258

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

244944

AF XY:

0.00000755

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1459090

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

725572

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33420

American (AMR)

AF:

0.00

AC:

AN:

44480

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.0000350

AC:

AN:

85634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53098

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1110742

Other (OTH)

AF:

0.0000664

AC:

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.0000197

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41600

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2116

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

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:

0.0000667

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000247

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

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.041

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.2

PhyloP100

4.5

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.94

REVEL

Benign

0.14

Sift

Benign

0.079

Sift4G

Benign

0.27

Polyphen

1.0

Vest4

0.63

MutPred

0.30

Gain of ubiquitination at E174 (P = 0.0025)

MVP

0.52

MPC

0.26

ClinPred

0.47

GERP RS

5.1

Varity_R

0.14

gMVP

0.32

Mutation Taster

=94/6

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