14-94115853-C-T

Position:

• chr14-94115853-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001130080.3(IFI27):​c.194C>T​(p.Ser65Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,450,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IFI27 NM_001130080.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.79

Genes affected

IFI27 (HGNC:5397): (interferon alpha inducible protein 27) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity; identical protein binding activity; and lamin binding activity. Involved in several processes, including cellular protein metabolic process; defense response to other organism; and extrinsic apoptotic signaling pathway. Acts upstream of or within negative regulation of transcription by RNA polymerase II and regulation of protein export from nucleus. Located in mitochondrial membrane and nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

IFI27 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFI27	NM_001130080.3	c.194C>T	p.Ser65Phe	missense_variant	4/5		NP_001123552.1
IFI27	NM_001288952.2	c.194C>T	p.Ser65Phe	missense_variant	5/6		NP_001275881.1
IFI27	NM_001288956.2	c.194C>T	p.Ser65Phe	missense_variant	4/5		NP_001275885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFI27	ENST00000621160.5	c.194C>T	p.Ser65Phe	missense_variant	4/5	1		ENSP00000483498.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1450906 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 720658

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

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

Nov 10, 2024

The c.185C>T (p.S62F) alteration is located in exon 4 (coding exon 3) of the IFI27 gene. This alteration results from a C to T substitution at nucleotide position 185, causing the serine (S) at amino acid position 62 to be replaced by a phenylalanine (F). 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	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.31	T;.;.;.;.;.;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.62	T;D;D;D;.;D;.;D
M_CAP	Benign	0.077	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.052	T
PrimateAI	Uncertain	0.51	T
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D
Vest4		0.83, 0.77, 0.82
MutPred		0.62		.;.;.;.;.;.;.;Loss of disorder (P = 0.0014);
MVP		0.42
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.47
gMVP		0.68

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: chr14-94582190;