10-89402292-A-T

Position:

chr10-89402292-A-T

Variant summary

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

The NM_001270928.2(IFIT1):c.-77A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000423 in 1,607,602 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 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

IFIT1
NM_001270928.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.05

Variant links:

Genes affected

IFIT1 (HGNC:5407): (interferon induced protein with tetratricopeptide repeats 1) This gene encodes a protein containing tetratricopeptide repeats that was originally identified as induced upon treatment with interferon. The encoded protein may inhibit viral replication and translational initiation. This gene is located in a cluster on chromosome 10 with five other closely related genes. There is a pseudogene for this gene on chromosome 13. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2012]

IFIT1 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:

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=0.12426862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFIT1	NM_001548.5 linkuse as main transcript	c.17A>T	p.Asp6Val	missense_variant	2/2	ENST00000371804.4	NP_001539.3	P09914-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IFIT1	ENST00000371804.4 linkuse as main transcript	c.17A>T	p.Asp6Val	missense_variant	2/2	1	NM_001548.5	ENSP00000360869.3	P09914-1
IFIT1	ENST00000546318 linkuse as main transcript	c.-77A>T		5_prime_UTR_premature_start_codon_gain_variant	3/3	3		ENSP00000441968.1	P09914-2
IFIT1	ENST00000546318 linkuse as main transcript	c.-77A>T		5_prime_UTR_variant	3/3	3		ENSP00000441968.1	P09914-2
LIPA	ENST00000371837.5 linkuse as main transcript	c.61+10499T>A		intron_variant		2		ENSP00000360903.1	P38571-2

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000324

AC:

AN:

246570

Hom.:

AF XY:

0.0000375

AC XY:

AN XY:

133360

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.0000297

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:

0.0000234

AC:

AN:

1455260

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

723928

show subpopulations

Gnomad4 AFR exome

AF:

0.000905

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.000223

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000769

Gnomad4 AMR

AF:

0.000131

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:

0.0000756

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Aug 29, 2023

The c.17A>T (p.D6V) alteration is located in exon 2 (coding exon 2) of the IFIT1 gene. This alteration results from a A to T substitution at nucleotide position 17, causing the aspartic acid (D) at amino acid position 6 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

0.078

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.55

M_CAP

Benign

0.0087

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.097

Sift

Uncertain

0.024

Sift4G

Benign

0.093

Polyphen

0.97

Vest4

0.39

MVP

0.40

MPC

0.31

ClinPred

0.15

GERP RS

0.74

Varity_R

0.14

gMVP

0.17

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