Genetic Variant IFITM3:p.Pro41Arg (chr11-320692-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021034.3(IFITM3):c.122C>G(p.Pro41Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P41T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IFITM3
NM_021034.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.555

Publications

1 publications found

Variant links:

Genes affected

IFITM3 (HGNC:5414): (interferon induced transmembrane protein 3) Interferon-induced transmembrane (IFITM) proteins are a family of interferon induced antiviral proteins. The family contains five members, including IFITM1, IFITM2 and IFITM3 and belong to the CD225 superfamily. The protein encoded by this gene restricts cellular entry by diverse viral pathogens, such as influenza A virus, Ebola virus and Sars-CoV-2. [provided by RefSeq, Nov 2021]

IFITM3 links:

IFITM3-AS1 (HGNC:58185):

IFITM3-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16409227).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021034.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFITM3	NM_021034.3	MANE Select	c.122C>G	p.Pro41Arg	missense	Exon 1 of 2	NP_066362.2	Q01628
	IFITM3	NR_049759.2		n.169C>G		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFITM3	ENST00000399808.5	TSL:1 MANE Select	c.122C>G	p.Pro41Arg	missense	Exon 1 of 2	ENSP00000382707.4	Q01628
IFITM3-AS1	ENST00000602429.2	TSL:1	n.115+1946G>C		intron	N/A
IFITM3	ENST00000926220.1		c.122C>G	p.Pro41Arg	missense	Exon 1 of 2	ENSP00000596279.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461540

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111844

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.1

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.081

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.056

M_CAP

Benign

0.080

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.5

PhyloP100

-0.56

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.25

Sift

Benign

0.59

Sift4G

Benign

0.35

Polyphen

0.99

Vest4

0.058

MutPred

0.38

Loss of glycosylation at P41 (P = 0.0049)

MVP

0.69

MPC

0.79

ClinPred

0.44

GERP RS

-1.3

PromoterAI

0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.046

gMVP

0.19

Mutation Taster

=100/0

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

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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