Variant 11-1747809-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001170820.4(IFITM10):c.395A>C(p.Lys132Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000484 in 1,550,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

IFITM10
NM_001170820.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.77

Variant links:

Genes affected

IFITM10 (HGNC:40022): (interferon induced transmembrane protein 10) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

IFITM10 links:

ENSG00000250644 (HGNC:):

ENSG00000250644 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0118635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFITM10	NM_001170820.4 linkuse as main transcript	c.395A>C	p.Lys132Thr	missense_variant	2/3	ENST00000340134.5	NP_001164291.2	A6NMD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFITM10	ENST00000340134.5 linkuse as main transcript	c.395A>C	p.Lys132Thr	missense_variant	2/3	3	NM_001170820.4	ENSP00000344430.4		A6NMD0
ENSG00000250644	ENST00000636615.1 linkuse as main transcript	c.1382A>C	p.Lys461Thr	missense_variant	9/10	5		ENSP00000490014.1		A0A1B0GU92

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000717

AC:

AN:

153370

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

81176

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000449

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000365

AC:

AN:

1397852

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

689370

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.000591

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000759

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000186

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.000158

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.000147

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000677

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

Feb 28, 2023

The c.395A>C (p.K132T) alteration is located in exon 2 (coding exon 2) of the IFITM10 gene. This alteration results from a A to C substitution at nucleotide position 395, causing the lysine (K) at amino acid position 132 to be replaced by a threonine (T). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.094

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.90

L;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.0

N;.;.

REVEL

Benign

0.049

Sift

Uncertain

0.0050

D;.;.

Sift4G

Uncertain

0.038

D;.;.

Vest4

0.44

MutPred

0.41

Loss of methylation at K132 (P = 0.0028);.;.;

MVP

0.24

ClinPred

0.21

GERP RS

2.6

Varity_R

0.28

gMVP

0.48

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