NM_206949.3:c.178G>T

Variant names:

• chr14-94101930-G-T
• rs200925095
• NM_206949.3:c.178G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_206949.3(IFI27L1):​c.178G>T​(p.Gly60Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 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: 6.8e-7 (0 hom.)
• Consequence: IFI27L1 NM_206949.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.48

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI27L1	NM_206949.3	c.178G>T	p.Gly60Cys	missense_variant	Exon 4 of 5	ENST00000555523.6	NP_996832.1
IFI27L1	NM_145249.3	c.178G>T	p.Gly60Cys	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.178G>T	p.Gly60Cys	missense_variant	Exon 4 of 5	2	NM_206949.3	ENSP00000451851.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.34	T;T;.;.;.;.
Eigen	Benign	-0.0048
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.81	D;D;D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Pathogenic	3.7	H;H;.;.;.;.
PROVEAN	Pathogenic	-8.9	D;D;D;D;D;D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D
Polyphen		1.0	D;D;.;.;.;.
Vest4		0.70
MutPred		0.66		Gain of catalytic residue at V62 (P = 0);Gain of catalytic residue at V62 (P = 0);.;.;.;Gain of catalytic residue at V62 (P = 0);
MVP		0.27
MPC		0.29
ClinPred		1.0	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.81
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200925095; hg19: chr14-94568276;