5-149300300-A-G

Variant names:

• chr5-149300300-A-G
• rs781212886
• NM_152406.4:c.175A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152406.4(AFAP1L1):​c.175A>G​(p.Thr59Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,288 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AFAP1L1 NM_152406.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFAP1L1	NM_152406.4	c.175A>G	p.Thr59Ala	missense_variant	Exon 3 of 19	ENST00000296721.9	NP_689619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFAP1L1	ENST00000296721.9	c.175A>G	p.Thr59Ala	missense_variant	Exon 3 of 19	1	NM_152406.4	ENSP00000296721.4
AFAP1L1	ENST00000515000.1	c.175A>G	p.Thr59Ala	missense_variant	Exon 3 of 18	1		ENSP00000424427.1
AFAP1L1	ENST00000455574.6	n.273A>G		non_coding_transcript_exon_variant	Exon 3 of 9	1
AFAP1L1	ENST00000522492.1	n.249A>G		non_coding_transcript_exon_variant	Exon 3 of 8	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250456 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135322

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461288 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726854

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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	0.082
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.14
Sift	Benign	0.049	D;D
Sift4G	Benign	0.22	T;T
Polyphen		0.94	P;P
Vest4		0.66
MutPred		0.34		Loss of glycosylation at T59 (P = 0.0493);Loss of glycosylation at T59 (P = 0.0493);
MVP		0.71
MPC		0.13
ClinPred		0.62	D
GERP RS		5.0
Varity_R		0.14
gMVP		0.37

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: rs781212886; hg19: chr5-148679863;