Variant 5-149306330-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152406.4(AFAP1L1):c.461T>C(p.Ile154Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AFAP1L1
NM_152406.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.53

Variant links:

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]

AFAP1L1 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
AFAP1L1	NM_152406.4 link	c.461T>C	p.Ile154Thr	missense_variant	6/19	ENST00000296721.9	NP_689619.1	Q8TED9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AFAP1L1	ENST00000296721.9 link	c.461T>C	p.Ile154Thr	missense_variant	6/19	1	NM_152406.4	ENSP00000296721.4	Q8TED9-1
AFAP1L1	ENST00000515000.1 link	c.461T>C	p.Ile154Thr	missense_variant	6/18	1		ENSP00000424427.1	Q8TED9-2
AFAP1L1	ENST00000455574.6 link	n.559T>C		non_coding_transcript_exon_variant	6/9	1
AFAP1L1	ENST00000522492.1 link	n.585T>C		non_coding_transcript_exon_variant	7/8	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461114

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726770

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2024

The c.461T>C (p.I154T) alteration is located in exon 6 (coding exon 6) of the AFAP1L1 gene. This alteration results from a T to C substitution at nucleotide position 461, causing the isoleucine (I) at amino acid position 154 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.18

B;P

Vest4

0.76

MutPred

0.20

Loss of stability (P = 0.0095);Loss of stability (P = 0.0095);

MVP

0.54

MPC

0.17

ClinPred

0.86

GERP RS

5.3

Varity_R

0.098

gMVP

0.36

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over