10-89403054-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001548.5(IFIT1):​c.779T>A​(p.Phe260Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,614,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

IFIT1
NM_001548.5 missense

Scores

11
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32278436).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IFIT1NM_001548.5 linkuse as main transcriptc.779T>A p.Phe260Tyr missense_variant 2/2 ENST00000371804.4 NP_001539.3 P09914-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IFIT1ENST00000371804.4 linkuse as main transcriptc.779T>A p.Phe260Tyr missense_variant 2/21 NM_001548.5 ENSP00000360869.3 P09914-1
IFIT1ENST00000546318.2 linkuse as main transcriptc.686T>A p.Phe229Tyr missense_variant 3/33 ENSP00000441968.1 P09914-2
LIPAENST00000371837.5 linkuse as main transcriptc.61+9737A>T intron_variant 2 ENSP00000360903.1 P38571-2

Frequencies

GnomAD3 genomes
AF:
0.000309
AC:
47
AN:
152186
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000676
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000267
AC:
67
AN:
251142
Hom.:
0
AF XY:
0.000258
AC XY:
35
AN XY:
135780
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000546
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000287
AC:
419
AN:
1461888
Hom.:
1
Cov.:
34
AF XY:
0.000309
AC XY:
225
AN XY:
727246
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:
0.00
Gnomad4 FIN exome
AF:
0.000168
Gnomad4 NFE exome
AF:
0.000351
Gnomad4 OTH exome
AF:
0.000281
GnomAD4 genome
AF:
0.000309
AC:
47
AN:
152186
Hom.:
0
Cov.:
33
AF XY:
0.000296
AC XY:
22
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000676
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000573
Hom.:
0
Bravo
AF:
0.000264
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.000305
AC:
37
EpiCase
AF:
0.000654
EpiControl
AF:
0.000296

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 submitterclinical testingAmbry GeneticsAug 01, 2024The c.779T>A (p.F260Y) alteration is located in exon 2 (coding exon 2) of the IFIT1 gene. This alteration results from a T to A substitution at nucleotide position 779, causing the phenylalanine (F) at amino acid position 260 to be replaced by a tyrosine (Y). 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
0.14
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T;.
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.71
T;T
M_CAP
Uncertain
0.24
D
MetaRNN
Benign
0.32
T;T
MetaSVM
Uncertain
0.25
D
MutationAssessor
Uncertain
2.4
M;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.5
D;D
REVEL
Uncertain
0.58
Sift
Benign
0.10
T;T
Sift4G
Benign
0.089
T;T
Polyphen
1.0
D;.
Vest4
0.46
MVP
0.78
MPC
0.36
ClinPred
0.26
T
GERP RS
5.6
Varity_R
0.55
gMVP
0.27

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.

Other links and lift over

dbSNP: rs148306581; hg19: chr10-91162811; API