Variant chr9-131096634-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The ENST00000247291.8(AIF1L):c.5C>T(p.Ser2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 1,332,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

AIF1L
ENST00000247291.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

Variant links:

Genes affected

AIF1L (HGNC:28904): (allograft inflammatory factor 1 like) Enables actin filament binding activity. Predicted to be involved in actin filament bundle assembly and ruffle assembly. Located in actin cytoskeleton and focal adhesion. Colocalizes with actin filament. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

AIF1L links:

AIF1L (HGNC:):

AIF1L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity AIF1L_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIF1L	NM_031426.4 linkuse as main transcript	c.5C>T	p.Ser2Leu	missense_variant	1/6	ENST00000247291.8	NP_113614.1	Q9BQI0-1
AIF1L	NM_001185095.2 linkuse as main transcript	c.5C>T	p.Ser2Leu	missense_variant	1/7		NP_001172024.1	Q9BQI0-2
AIF1L	NM_001185096.2 linkuse as main transcript	c.5C>T	p.Ser2Leu	missense_variant	1/6		NP_001172025.1	Q9BQI0-4
AIF1L	NR_033701.2 linkuse as main transcript	n.104C>T		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIF1L	ENST00000247291.8 linkuse as main transcript	c.5C>T	p.Ser2Leu	missense_variant	1/6	1	NM_031426.4	ENSP00000247291.3		Q9BQI0-1
AIF1L	ENST00000372302.5 linkuse as main transcript	c.5C>T	p.Ser2Leu	missense_variant	1/6	2		ENSP00000361376.1		Q9BQI0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000450

AC:

AN:

1332030

Hom.:

Cov.:

AF XY:

0.00000761

AC XY:

AN XY:

657076

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:

0.0000136

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000473

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jan 06, 2023

The c.5C>T (p.S2L) alteration is located in exon 1 (coding exon 1) of the AIF1L gene. This alteration results from a C to T substitution at nucleotide position 5, causing the serine (S) at amino acid position 2 to be replaced by a leucine (L). 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

0.21

BayesDel_addAF

Benign

-0.0052

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0029

.;T;.;.;.

Eigen

Benign

0.0075

Eigen_PC

Benign

0.032

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.51

T;T;T;T;T

M_CAP

Pathogenic

0.65

MetaRNN

Uncertain

0.47

T;T;T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.5

L;L;L;L;.

MutationTaster

Benign

0.78

D;D;D;D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Uncertain

0.019

D;T;T;T;T

Polyphen

1.0

D;D;.;P;.

Vest4

0.24

MutPred

0.22

Gain of stability (P = 0.0053);Gain of stability (P = 0.0053);Gain of stability (P = 0.0053);Gain of stability (P = 0.0053);Gain of stability (P = 0.0053);

MVP

0.77

MPC

0.39

ClinPred

0.90

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.32

gMVP

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over