dbSNP rs1292168593: AFAP1:p.Val723Phe (chr4-7772906-C-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_001134647.2(AFAP1):c.2167G>T(p.Val723Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V723I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AFAP1
NM_001134647.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.52

Publications

0 publications found

Variant links:

Genes affected

AFAP1 (HGNC:24017): (actin filament associated protein 1) The protein encoded by this gene is a Src binding partner. It may represent a potential modulator of actin filament integrity in response to cellular signals, and may function as an adaptor protein by linking Src family members and/or other signaling proteins to actin filaments. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

AFAP1 links:

AFAP1-AS1 (HGNC:28141): (AFAP1 antisense RNA 1) This gene produces a long non-coding RNA that is overexpressed in tumor cells and may promote cancer cell metastasis. [provided by RefSeq, Dec 2017]

AFAP1-AS1 links:

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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_001134647.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AFAP1	NM_001134647.2	MANE Select	c.2167G>T	p.Val723Phe	missense	Exon 16 of 18	NP_001128119.1	Q8N556-2
AFAP1	NM_001371090.1		c.1915G>T	p.Val639Phe	missense	Exon 14 of 16	NP_001358019.1	Q8N556-1
AFAP1	NM_001371091.1		c.1915G>T	p.Val639Phe	missense	Exon 16 of 18	NP_001358020.1	Q8N556-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AFAP1	ENST00000420658.6	TSL:2 MANE Select	c.2167G>T	p.Val723Phe	missense	Exon 16 of 18	ENSP00000410689.1	Q8N556-2
AFAP1	ENST00000360265.9	TSL:1	c.1915G>T	p.Val639Phe	missense	Exon 14 of 16	ENSP00000353402.4	Q8N556-1
AFAP1-AS1	ENST00000608442.2	TSL:1	n.786C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112002

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Uncertain

0.099

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.88

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.097

MetaRNN

Uncertain

0.72

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.9

PhyloP100

4.5

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.76

MutPred

0.23

Gain of glycosylation at S642 (P = 0.029)

MVP

0.59

MPC

0.44

ClinPred

0.99

GERP RS

4.0

Varity_R

0.84

gMVP

0.45

Mutation Taster

=64/36

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over