10-89403054-T-A
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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
NM_001548.5 missense
Scores
11
8
Clinical Significance
Conservation
PhyloP100: 3.18
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]
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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 |
---|---|---|---|---|---|---|---|---|
IFIT1 | NM_001548.5 | c.779T>A | p.Phe260Tyr | missense_variant | 2/2 | ENST00000371804.4 | NP_001539.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IFIT1 | ENST00000371804.4 | c.779T>A | p.Phe260Tyr | missense_variant | 2/2 | 1 | NM_001548.5 | ENSP00000360869.3 | ||
IFIT1 | ENST00000546318.2 | c.686T>A | p.Phe229Tyr | missense_variant | 3/3 | 3 | ENSP00000441968.1 | |||
LIPA | ENST00000371837.5 | c.61+9737A>T | intron_variant | 2 | ENSP00000360903.1 |
Frequencies
GnomAD3 genomes AF: 0.000309 AC: 47AN: 152186Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000267 AC: 67AN: 251142Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135780
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GnomAD4 exome AF: 0.000287 AC: 419AN: 1461888Hom.: 1 Cov.: 34 AF XY: 0.000309 AC XY: 225AN XY: 727246
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GnomAD4 genome AF: 0.000309 AC: 47AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.000296 AC XY: 22AN XY: 74356
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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 01, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at