5-149301220-G-C

Variant names:

• chr5-149301220-G-C
• rs199689420
• NM_152406.4:c.317G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152406.4(AFAP1L1):​c.317G>C​(p.Arg106Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. R106L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AFAP1L1 NM_152406.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031505823).

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.317G>C	p.Arg106Pro	missense	Exon 4 of 19	NP_689619.1	Q8TED9-1
	AFAP1L1	NM_001323062.2		c.317G>C	p.Arg106Pro	missense	Exon 4 of 18	NP_001309991.1
	AFAP1L1	NM_001146337.3		c.317G>C	p.Arg106Pro	missense	Exon 4 of 18	NP_001139809.1	Q8TED9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1L1	ENST00000296721.9	TSL:1 MANE Select	c.317G>C	p.Arg106Pro	missense	Exon 4 of 19	ENSP00000296721.4	Q8TED9-1
	AFAP1L1	ENST00000515000.1	TSL:1	c.317G>C	p.Arg106Pro	missense	Exon 4 of 18	ENSP00000424427.1	Q8TED9-2
	AFAP1L1	ENST00000455574.6	TSL:1	n.415G>C		non_coding_transcript_exon	Exon 4 of 9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.71
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.00095	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.0010
PrimateAI	Benign	0.23	T
PROVEAN	Benign	2.7	N
REVEL	Benign	0.064
Sift	Benign	0.34	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.051
MutPred		0.16		Gain of catalytic residue at P105 (P = 0.0186)
MVP		0.13
MPC		0.14
ClinPred		0.037	T
GERP RS		1.6
Varity_R		0.062
gMVP		0.19
Mutation Taster		=98/2	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: rs199689420; hg19: chr5-148680783;