Genetic Variant NM_001623.5:c.169T>C (chr6-31616118-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001623.5(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
NM_001623.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37

Publications

0 publications found

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:

ENSG00000289375 (HGNC:):

ENSG00000289375 links:

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ACMG classification

Classification was made for transcript

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_001623.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AIF1	NM_001623.5	MANE Select	c.169T>C	p.Phe57Leu	missense	Exon 4 of 6	NP_001614.3
AIF1	NM_001318970.2		c.7T>C	p.Phe3Leu	missense	Exon 4 of 6	NP_001305899.1	P55008-2
AIF1	NM_032955.3		c.7T>C	p.Phe3Leu	missense	Exon 1 of 3	NP_116573.1	I3WTX1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AIF1	ENST00000376059.8	TSL:1 MANE Select	c.169T>C	p.Phe57Leu	missense	Exon 4 of 6	ENSP00000365227.3	P55008-1
AIF1	ENST00000337917.11	TSL:1	c.211T>C	p.Phe71Leu	missense	Exon 4 of 6	ENSP00000338776.7	Q5STX8
AIF1	ENST00000376049.4	TSL:1	c.7T>C	p.Phe3Leu	missense	Exon 1 of 3	ENSP00000365217.4	P55008-2

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

African (AFR)

AF:

0.00

AC:

AN:

33238

American (AMR)

AF:

0.00

AC:

AN:

43646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24764

East Asian (EAS)

AF:

0.00

AC:

AN:

39528

South Asian (SAS)

AF:

0.00

AC:

AN:

83752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103006

Other (OTH)

AF:

0.00

AC:

AN:

59728

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.037

Eigen_PC

Benign

0.00022

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.86

MutationAssessor

Benign

2.0

PhyloP100

7.4

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.28

Sift

Benign

0.034

Sift4G

Uncertain

0.0090

Polyphen

0.17

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

PromoterAI

-0.0018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.21

gMVP

0.73

Mutation Taster

=67/33

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over