5-149301189-G-T

Variant names:

• chr5-149301189-G-T
• rs1323240480
• NM_152406.4:c.286G>T

Variant summary

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

The NM_152406.4(AFAP1L1):​c.286G>T​(p.Gly96*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AFAP1L1 NM_152406.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• 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.286G>T	p.Gly96*	stop_gained	Exon 4 of 19	NP_689619.1	Q8TED9-1
	AFAP1L1	NM_001323062.2		c.286G>T	p.Gly96*	stop_gained	Exon 4 of 18	NP_001309991.1
	AFAP1L1	NM_001146337.3		c.286G>T	p.Gly96*	stop_gained	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.286G>T	p.Gly96*	stop_gained	Exon 4 of 19	ENSP00000296721.4	Q8TED9-1
	AFAP1L1	ENST00000515000.1	TSL:1	c.286G>T	p.Gly96*	stop_gained	Exon 4 of 18	ENSP00000424427.1	Q8TED9-2
	AFAP1L1	ENST00000455574.6	TSL:1	n.384G>T		non_coding_transcript_exon	Exon 4 of 9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.77	D
PhyloP100		1.8
Vest4		0.25
GERP RS		2.5
Mutation Taster		=15/185	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1323240480; hg19: chr5-148680752;