5-149301220-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AFAP1L1 NM_152406.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFAP1L1	NM_152406.4	c.317G>C	p.Arg106Pro	missense_variant	Exon 4 of 19	ENST00000296721.9	NP_689619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFAP1L1	ENST00000296721.9	c.317G>C	p.Arg106Pro	missense_variant	Exon 4 of 19	1	NM_152406.4	ENSP00000296721.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.032	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	2.7	N;N
REVEL	Benign	0.064
Sift	Benign	0.34	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;B
Vest4		0.051
MutPred		0.16		Gain of catalytic residue at P105 (P = 0.0186);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

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

LitVar

Other links and lift over

dbSNP: rs199689420; hg19: chr5-148680783;