Variant 10-89418238-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012420.3(IFIT5):c.1039A>G(p.Met347Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,614,084 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

IFIT5
NM_012420.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Variant links:

Genes affected

IFIT5 (HGNC:13328): (interferon induced protein with tetratricopeptide repeats 5) Enables nucleic acid binding activity. Involved in defense response to virus; negative regulation of viral genome replication; and positive regulation of I-kappaB kinase/NF-kappaB signaling. Located in actin cytoskeleton; apical part of cell; and ruffle membrane. Colocalizes with IkappaB kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

IFIT5 links:

LOC107984251 (HGNC:):

LOC107984251 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19364637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFIT5	NM_012420.3 linkuse as main transcript	c.1039A>G	p.Met347Val	missense_variant	2/2	ENST00000371795.5	NP_036552.1
LOC107984251	XR_001747541.2 linkuse as main transcript	n.74-2433T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFIT5	ENST00000371795.5 linkuse as main transcript	c.1039A>G	p.Met347Val	missense_variant	2/2	1	NM_012420.3	ENSP00000360860	P1	Q13325-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

251440

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000237

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000131

AC:

191

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000159

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000125

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000298

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000115

AC:

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

Sep 27, 2022

The c.1039A>G (p.M347V) alteration is located in exon 2 (coding exon 2) of the IFIT5 gene. This alteration results from a A to G substitution at nucleotide position 1039, causing the methionine (M) at amino acid position 347 to be replaced by a valine (V). 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

0.20

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.74

M_CAP

Benign

0.0069

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.69

N;N

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.16

Sift

Benign

0.14

Sift4G

Benign

0.11

Polyphen

0.66

Vest4

0.24

MVP

0.59

MPC

0.23

ClinPred

0.16

GERP RS

6.0

Varity_R

0.51

gMVP

0.30

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

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