14-94101954-G-C

Variant names:

• chr14-94101954-G-C
• NM_206949.3:c.202G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_206949.3(IFI27L1):​c.202G>C​(p.Val68Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFI27L1 NM_206949.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.67

Genes affected

IFI27L1 (HGNC:19754): (interferon alpha inducible protein 27 like 1) Involved in apoptotic process. Predicted to be integral component of membrane. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.37724546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI27L1	NM_206949.3	c.202G>C	p.Val68Leu	missense_variant	Exon 4 of 5	ENST00000555523.6	NP_996832.1
IFI27L1	NM_145249.3	c.202G>C	p.Val68Leu	missense_variant	Exon 4 of 5		NP_660292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFI27L1	ENST00000555523.6	c.202G>C	p.Val68Leu	missense_variant	Exon 4 of 5	2	NM_206949.3	ENSP00000451851.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.202G>C (p.V68L) alteration is located in exon 4 (coding exon 3) of the IFI27L1 gene. This alteration results from a G to C substitution at nucleotide position 202, causing the valine (V) at amino acid position 68 to be replaced by a leucine (L). 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	0.61
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	18
DANN	Benign	0.93
Eigen	Benign	-0.0086
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.64	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.23
Sift4G	Pathogenic	0.0	D
Vest4		0.41
MutPred		0.33		Loss of glycosylation at S89 (P = 0.0453);
MVP		0.25
ClinPred		0.99	D
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: chr14-94568300;