NM_001134647.2:c.2432A>G

Variant names:

• chr4-7763778-T-C
• NM_001134647.2:c.2432A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001134647.2(AFAP1):​c.2432A>G​(p.Lys811Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,399,408 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AFAP1 NM_001134647.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66
• Publications: 0 publications found

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1	NM_001134647.2	MANE Select	c.2432A>G	p.Lys811Arg	missense	Exon 18 of 18	NP_001128119.1	Q8N556-2
	AFAP1	NM_001371090.1		c.2180A>G	p.Lys727Arg	missense	Exon 16 of 16	NP_001358019.1	Q8N556-1
	AFAP1	NM_001371091.1		c.2180A>G	p.Lys727Arg	missense	Exon 18 of 18	NP_001358020.1	Q8N556-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1	ENST00000420658.6	TSL:2 MANE Select	c.2432A>G	p.Lys811Arg	missense	Exon 18 of 18	ENSP00000410689.1	Q8N556-2
	AFAP1	ENST00000360265.9	TSL:1	c.2180A>G	p.Lys727Arg	missense	Exon 16 of 16	ENSP00000353402.4	Q8N556-1
	AFAP1-AS1	ENST00000608442.2	TSL:1	n.84-8426T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399408 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690238

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35742

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078932

Other (OTH) AF: 0.00 AC: 0 AN: 58000

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.7
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.21
Sift	Uncertain	0.015	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.29		Loss of methylation at K727 (P = 0.0233)
MVP		0.22
MPC		0.40
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.17
gMVP		0.37
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.27		Position offset: 13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr4-7765505;