5-149306389-G-C

Variant names:

• chr5-149306389-G-C
• rs550069903
• NM_152406.4:c.520G>C

Variant summary

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

The NM_152406.4(AFAP1L1):​c.520G>C​(p.Glu174Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. E174K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AFAP1L1 NM_152406.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46
• Publications: 0 publications found

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]

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_152406.4. 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
	AFAP1L1	NM_152406.4	MANE Select	c.520G>C	p.Glu174Gln	missense	Exon 6 of 19	NP_689619.1	Q8TED9-1
	AFAP1L1	NM_001146337.3		c.520G>C	p.Glu174Gln	missense	Exon 6 of 18	NP_001139809.1	Q8TED9-2
	AFAP1L1	NM_001323063.2		c.520G>C	p.Glu174Gln	missense	Exon 6 of 9	NP_001309992.1	Q8TED9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1L1	ENST00000296721.9	TSL:1 MANE Select	c.520G>C	p.Glu174Gln	missense	Exon 6 of 19	ENSP00000296721.4	Q8TED9-1
	AFAP1L1	ENST00000515000.1	TSL:1	c.520G>C	p.Glu174Gln	missense	Exon 6 of 18	ENSP00000424427.1	Q8TED9-2
	AFAP1L1	ENST00000455574.6	TSL:1	n.618G>C		non_coding_transcript_exon	Exon 6 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.5
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.093
Sift	Benign	0.046	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.25		Loss of sheet (P = 0.0457)
MVP		0.60
MPC		0.39
ClinPred		0.77	D
GERP RS		5.1
Varity_R		0.12
gMVP		0.30
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs550069903; hg19: chr5-148685952;