Genetic Variant AFAP1:p.Ser795Cys (chr4-7768878-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_001134647.2(AFAP1):c.2384C>G(p.Ser795Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,584 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. S795F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AFAP1
NM_001134647.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.86

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.2384C>G	p.Ser795Cys	missense	Exon 17 of 18	NP_001128119.1	Q8N556-2
AFAP1	NM_001371090.1		c.2132C>G	p.Ser711Cys	missense	Exon 15 of 16	NP_001358019.1	Q8N556-1
AFAP1	NM_001371091.1		c.2132C>G	p.Ser711Cys	missense	Exon 17 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.2384C>G	p.Ser795Cys	missense	Exon 17 of 18	ENSP00000410689.1	Q8N556-2
AFAP1	ENST00000360265.9	TSL:1	c.2132C>G	p.Ser711Cys	missense	Exon 15 of 16	ENSP00000353402.4	Q8N556-1
AFAP1-AS1	ENST00000608442.2	TSL:1	n.84-3326G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000805

AC:

AN:

248396

AF XY:

0.0000149

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:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455584

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33332

American (AMR)

AF:

0.00

AC:

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.00

AC:

AN:

86006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1107452

Other (OTH)

AF:

0.00

AC:

AN:

60048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

M_CAP

Benign

0.0093

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.5

PhyloP100

6.9

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.1

REVEL

Benign

0.20

Sift

Uncertain

0.0060

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.65

MutPred

0.27

Loss of glycosylation at P708 (P = 0.0238)

MVP

0.36

MPC

0.32

ClinPred

0.83

GERP RS

4.0

Varity_R

0.15

gMVP

0.32

Mutation Taster

=80/20

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over