10-89417931-A-C

Position:

• chr10-89417931-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012420.3(IFIT5):​c.732A>C​(p.Gln244His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IFIT5 NM_012420.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.685

Genes affected

IFIT5 (HGNC:13328): (interferon induced protein with tetratricopeptide repeats 5) Enables nucleic acid binding activity. Involved in defense response to virus; negative regulation of viral genome replication; and positive regulation of I-kappaB kinase/NF-kappaB signaling. Located in actin cytoskeleton; apical part of cell; and ruffle membrane. Colocalizes with IkappaB kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

LOC107984251 (HGNC:):

ACMG classification

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=0.11519045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFIT5	NM_012420.3	c.732A>C	p.Gln244His	missense_variant	2/2	ENST00000371795.5	NP_036552.1
LOC107984251	XR_001747541.2	n.74-2126T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFIT5	ENST00000371795.5	c.732A>C	p.Gln244His	missense_variant	2/2	1	NM_012420.3	ENSP00000360860.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2023

The c.732A>C (p.Q244H) alteration is located in exon 2 (coding exon 2) of the IFIT5 gene. This alteration results from a A to C substitution at nucleotide position 732, causing the glutamine (Q) at amino acid position 244 to be replaced by a histidine (H). 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	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.8
DANN	Benign	0.88
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.064	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.16
Sift	Benign	0.16	T
Sift4G	Benign	0.17	T
Polyphen		0.98	D
Vest4		0.25
MutPred		0.28		Gain of catalytic residue at Q244 (P = 0.0964);
MVP		0.39
MPC		0.61
ClinPred		0.73	D
GERP RS		-9.8
Varity_R		0.36
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-91177688;