4-7772873-C-G

Position:

• chr4-7772873-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001134647.2(AFAP1):​c.2200G>C​(p.Gly734Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AFAP1 NM_001134647.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.33

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-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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFAP1	NM_001134647.2	c.2200G>C	p.Gly734Arg	missense_variant	16/18	ENST00000420658.6	NP_001128119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFAP1	ENST00000420658.6	c.2200G>C	p.Gly734Arg	missense_variant	16/18	2	NM_001134647.2	ENSP00000410689.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.2200G>C (p.G734R) alteration is located in exon 16 (coding exon 15) of the AFAP1 gene. This alteration results from a G to C substitution at nucleotide position 2200, causing the glycine (G) at amino acid position 734 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T;T;.;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	.;D;D;.
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.0	M;M;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.5	D;D;D;D
REVEL	Uncertain	0.43
Sift	Benign	0.030	D;D;T;T
Sift4G	Uncertain	0.032	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.97
MutPred		0.45		Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);.;.;
MVP		0.39
MPC		0.52
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.41
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-7774600;