NM_001025295.3:c.80G>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001025295.3(IFITM5):c.80G>C(p.Gly27Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,556,868 control chromosomes in the GnomAD database, including 112,131 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17310 hom., cov: 32)

Exomes 𝑓: 0.35 ( 94821 hom. )

Consequence

IFITM5
NM_001025295.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.104

Variant links:

Genes affected

IFITM5 (HGNC:16644): (interferon induced transmembrane protein 5) This gene encodes a membrane protein thought to play a role in bone mineralization. This gene is located on chromosome 11 in a cluster of related genes which are induced by interferon, however, this gene has not been shown to be interferon inducible. A similar gene, located in a gene cluster on mouse chromosome 7, is a member of the interferon-inducible fragilis gene family. The mouse gene encodes a transmembrane protein described as participating in germ cell competence. A mutation in the 5' UTR of this gene has been associated with osteogenesis imperfecta type V (PMID: 22863190, 22863195). [provided by RefSeq, Aug 2012]

IFITM5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.3203142E-6).

BP6

Variant 11-299411-C-G is Benign according to our data. Variant chr11-299411-C-G is described in ClinVar as [Benign]. Clinvar id is 193131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-299411-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFITM5	NM_001025295.3 link	c.80G>C	p.Gly27Ala	missense_variant	Exon 1 of 2	ENST00000382614.2	NP_001020466.1	A6NNB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFITM5	ENST00000382614.2 link	c.80G>C	p.Gly27Ala	missense_variant	Exon 1 of 2	1	NM_001025295.3	ENSP00000372059.2		A6NNB3

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68267

AN:

151904

Hom.:

17267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.653

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.651

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.431

GnomAD3 exomes

AF:

0.451

AC:

76453

AN:

169550

Hom.:

19127

AF XY:

0.444

AC XY:

40519

AN XY:

91222

show subpopulations

Gnomad AFR exome

AF:

0.667

Gnomad AMR exome

AF:

0.628

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.653

Gnomad SAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.314

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.351

AC:

493297

AN:

1404846

Hom.:

94821

Cov.:

AF XY:

0.356

AC XY:

247238

AN XY:

695098

show subpopulations

Gnomad4 AFR exome

AF:

0.672

Gnomad4 AMR exome

AF:

0.611

Gnomad4 ASJ exome

AF:

0.349

Gnomad4 EAS exome

AF:

0.660

Gnomad4 SAS exome

AF:

0.563

Gnomad4 FIN exome

AF:

0.353

Gnomad4 NFE exome

AF:

0.305

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.450

AC:

68359

AN:

152022

Hom.:

17310

Cov.:

AF XY:

0.458

AC XY:

33987

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.653

Gnomad4 AMR

AF:

0.534

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.651

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.360

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.436

Alfa

AF:

0.261

Hom.:

1013

Bravo

AF:

0.472

ESP6500AA

AF:

0.598

AC:

2610

ESP6500EA

AF:

0.281

AC:

2407

ExAC

AF:

0.387

AC:

44760

Asia WGS

AF:

0.648

AC:

2252

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Osteogenesis imperfecta type 5

Benign:4

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 25, 2015

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:3

Mar 25, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.9

DANN

Benign

0.79

DEOGEN2

Benign

0.030

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0000063

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

REVEL

Benign

0.13

Sift

Benign

0.14

Sift4G

Benign

0.69

Polyphen

0.0060

Vest4

0.060

MPC

0.014

ClinPred

0.0084

GERP RS

2.3

Varity_R

0.045

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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