14-94115870-A-C

Variant names:

• chr14-94115870-A-C
• rs1887380641
• NM_001130080.3:c.211A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001130080.3(IFI27):​c.211A>C​(p.Met71Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M71I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IFI27 NM_001130080.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.03
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.814

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130080.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI27	NM_001130080.3	MANE Select	c.211A>C	p.Met71Leu	missense	Exon 4 of 5	NP_001123552.1	P40305-2
	IFI27	NM_001288952.2		c.211A>C	p.Met71Leu	missense	Exon 5 of 6	NP_001275881.1	P40305-2
	IFI27	NM_001288956.2		c.211A>C	p.Met71Leu	missense	Exon 4 of 5	NP_001275885.1	P40305-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI27	ENST00000621160.5	TSL:1 MANE Select	c.211A>C	p.Met71Leu	missense	Exon 4 of 5	ENSP00000483498.1	P40305-2
	IFI27	ENST00000612813.4	TSL:3	c.211A>C	p.Met71Leu	missense	Exon 4 of 5	ENSP00000483430.1	P40305-2
	IFI27	ENST00000616764.5	TSL:2	c.211A>C	p.Met71Leu	missense	Exon 5 of 6	ENSP00000477753.1	P40305-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449918 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 719990

African (AFR) AF: 0.00 AC: 0 AN: 33220

American (AMR) AF: 0.00 AC: 0 AN: 43378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25846

East Asian (EAS) AF: 0.00 AC: 0 AN: 39280

South Asian (SAS) AF: 0.00 AC: 0 AN: 84214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105902

Other (OTH) AF: 0.00 AC: 0 AN: 59948

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.64	T
PhyloP100		8.0
PrimateAI	Uncertain	0.58	T
Sift4G	Uncertain	0.0050	D
Vest4		0.63
MutPred		0.70		Loss of disorder (P = 0.0702)
MVP		0.44
ClinPred		0.98	D
GERP RS		3.5
Varity_R		0.43
gMVP		0.46
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs1887380641; hg19: chr14-94582207;