10-89339709-G-C

Position:

chr10-89339709-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001549.6(IFIT3):c.1054G>C(p.Val352Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00745 in 1,614,186 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 55 hom. )

Consequence

IFIT3
NM_001549.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.09

Variant links:

Genes affected

IFIT3 (HGNC:5411): (interferon induced protein with tetratricopeptide repeats 3) Enables identical protein binding activity. Involved in negative regulation of apoptotic process; negative regulation of cell population proliferation; and response to virus. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

IFIT3 links:

LIPA (HGNC:6617): (lipase A, lysosomal acid type) This gene encodes lipase A, the lysosomal acid lipase (also known as cholesterol ester hydrolase). This enzyme functions in the lysosome to catalyze the hydrolysis of cholesteryl esters and triglycerides. Mutations in this gene can result in Wolman disease and cholesteryl ester storage disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]

LIPA links:

LOC101926887 (HGNC:):

LOC101926887 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=0.0034144819).

BP6

Variant 10-89339709-G-C is Benign according to our data. Variant chr10-89339709-G-C is described in ClinVar as [Benign]. Clinvar id is 787590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00728 (10640/1461852) while in subpopulation MID AF= 0.0376 (217/5768). AF 95% confidence interval is 0.0335. There are 55 homozygotes in gnomad4_exome. There are 5319 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFIT3	NM_001549.6 link	c.1054G>C	p.Val352Leu	missense_variant	2/2	ENST00000371818.9	NP_001540.2	O14879Q5T765

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFIT3	ENST00000371818.9 link	c.1054G>C	p.Val352Leu	missense_variant	2/2	1	NM_001549.6	ENSP00000360883.4		O14879

Frequencies

GnomAD3 genomes

AF:

0.00904

AC:

1376

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00641

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00783

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.00765

AC:

1920

AN:

250858

Hom.:

AF XY:

0.00763

AC XY:

1034

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.00613

Gnomad ASJ exome

AF:

0.00756

Gnomad EAS exome

AF:

0.00267

Gnomad SAS exome

AF:

0.00464

Gnomad FIN exome

AF:

0.00643

Gnomad NFE exome

AF:

0.00889

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.00728

AC:

10640

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00731

AC XY:

5319

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0147

Gnomad4 AMR exome

AF:

0.00651

Gnomad4 ASJ exome

AF:

0.00819

Gnomad4 EAS exome

AF:

0.00194

Gnomad4 SAS exome

AF:

0.00394

Gnomad4 FIN exome

AF:

0.00672

Gnomad4 NFE exome

AF:

0.00729

Gnomad4 OTH exome

AF:

0.00901

GnomAD4 genome

AF:

0.00905

AC:

1378

AN:

152334

Hom.:

Cov.:

AF XY:

0.00853

AC XY:

635

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0142

Gnomad4 AMR

AF:

0.00640

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00327

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.00784

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00794

Hom.:

Bravo

AF:

0.00948

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.0125

AC:

ESP6500EA

AF:

0.00802

AC:

ExAC

AF:

0.00784

AC:

952

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00987

EpiControl

AF:

0.00966

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 24, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.023

DANN

Benign

0.47

DEOGEN2

Benign

0.0093

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.29

.;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.1

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.026

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.031

MVP

0.15

MPC

0.19

ClinPred

0.0042

GERP RS

-1.5

Varity_R

0.028

gMVP

0.058

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