Variant 14-94101957-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_206949.3(IFI27L1):c.205G>T(p.Ala69Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

IFI27L1
NM_206949.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.44

Variant links:

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]

IFI27L1 links:

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ACMG classification

Classification made for transcript

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=0.4191556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI27L1	NM_206949.3 link	c.205G>T	p.Ala69Ser	missense_variant	Exon 4 of 5	ENST00000555523.6	NP_996832.1	Q96BM0
IFI27L1	NM_145249.3 link	c.205G>T	p.Ala69Ser	missense_variant	Exon 4 of 5		NP_660292.1	Q96BM0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFI27L1	ENST00000555523.6 link	c.205G>T	p.Ala69Ser	missense_variant	Exon 4 of 5	2	NM_206949.3	ENSP00000451851.1		Q96BM0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251450

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

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.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.205G>T (p.A69S) alteration is located in exon 4 (coding exon 3) of the IFI27L1 gene. This alteration results from a G to T substitution at nucleotide position 205, causing the alanine (A) at amino acid position 69 to be replaced by a serine (S). 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

Benign

0.15

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.11

T;T;.;.;.;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.039

MetaRNN

Benign

0.42

T;T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.6

M;M;.;.;.;.

PROVEAN

Uncertain

-2.5

D;D;D;D;D;D

REVEL

Uncertain

0.30

Sift

Benign

0.10

T;T;T;T;T;T

Sift4G

Uncertain

0.052

T;T;D;D;D;D

Polyphen

1.0

D;D;.;.;.;.

Vest4

0.38

MutPred

0.61

Gain of catalytic residue at S66 (P = 0);Gain of catalytic residue at S66 (P = 0);.;.;.;Gain of catalytic residue at S66 (P = 0);

MVP

0.17

MPC

0.17

ClinPred

0.68

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over