14-94128517-C-G

Variant names:

• chr14-94128517-C-G
• rs201447722
• NM_032036.3:c.196G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032036.3(IFI27L2):​c.196G>C​(p.Val66Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V66M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFI27L2 NM_032036.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 0 publications found

Genes affected

IFI27L2 (HGNC:19753): (interferon alpha inducible protein 27 like 2) Involved in apoptotic process. Located in mitochondrial membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1755282).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032036.3. 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
	IFI27L2	NM_032036.3	MANE Select	c.196G>C	p.Val66Leu	missense	Exon 3 of 4	NP_114425.1	Q9H2X8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI27L2	ENST00000238609.4	TSL:1 MANE Select	c.196G>C	p.Val66Leu	missense	Exon 3 of 4	ENSP00000238609.3	Q9H2X8
	IFI27L2	ENST00000554909.1	TSL:1	n.461G>C		non_coding_transcript_exon	Exon 1 of 2
	IFI27L2	ENST00000555558.1	TSL:1	n.299G>C		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.89
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.21
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.069
Sift	Benign	0.39	T
Sift4G	Benign	0.23	T
Polyphen		0.95	P
Vest4		0.14
MutPred		0.35		Gain of catalytic residue at Q64 (P = 0.0194)
MVP		0.040
MPC		0.067
ClinPred		0.41	T
GERP RS		1.9
Varity_R		0.081
gMVP		0.56
Mutation Taster		=96/4	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: rs201447722; hg19: chr14-94594854;