Variant 6-31616118-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 ENST00000376059.8(AIF1):c.169T>C(p.Phe57Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AIF1
ENST00000376059.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37

Variant links:

Genes affected

AIF1 (HGNC:352): (allograft inflammatory factor 1) This gene encodes a protein that binds actin and calcium. This gene is induced by cytokines and interferon and may promote macrophage activation and growth of vascular smooth muscle cells and T-lymphocytes. Polymorphisms in this gene may be associated with systemic sclerosis. Alternative splicing results in multiple transcript variants, but the full-length and coding nature of some of these variants is not certain. [provided by RefSeq, Jan 2016]

AIF1 links:

Genome browser will be placed here

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
AIF1	NM_001623.5 linkuse as main transcript	c.169T>C	p.Phe57Leu	missense_variant	4/6	ENST00000376059.8	NP_001614.3
AIF1	NM_001318970.2 linkuse as main transcript	c.7T>C	p.Phe3Leu	missense_variant	4/6		NP_001305899.1
AIF1	NM_032955.3 linkuse as main transcript	c.7T>C	p.Phe3Leu	missense_variant	1/3		NP_116573.1
AIF1	XM_005248870.5 linkuse as main transcript	c.169T>C	p.Phe57Leu	missense_variant	4/4		XP_005248927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIF1	ENST00000376059.8 linkuse as main transcript	c.169T>C	p.Phe57Leu	missense_variant	4/6	1	NM_001623.5	ENSP00000365227	P1	P55008-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1445464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717504

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:

0.00

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

Dec 07, 2023

The c.7T>C (p.F3L) alteration is located in exon 3 (coding exon 1) of the AIF1 gene. This alteration results from a T to C substitution at nucleotide position 7, causing the phenylalanine (F) at amino acid position 3 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

Pathogenic

0.99

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;.;.

Eigen

Benign

-0.037

Eigen_PC

Benign

0.00022

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

2.0

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.1

D;D;D

REVEL

Benign

0.28

Sift

Benign

0.034

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.17

B;.;.

Vest4

0.92

MutPred

0.57

Gain of disorder (P = 0.1375);.;.;

MVP

0.57

MPC

0.19

ClinPred

0.77

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.21

gMVP

0.73

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