Genetic Variant NM_002171.2:c.395C>T (chr9-21206703-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002171.2(IFNA10):c.395C>T(p.Thr132Ile) 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. 14/21 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IFNA10
NM_002171.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.997

Variant links:

Genes affected

IFNA10 (HGNC:5418): (interferon alpha 10) This gene encodes a protein that belongs to the type I interferon family of proteins, and is located in a cluster of alpha interferon genes on chromosome 9. Interferons are small regulatory molecules that function in cell signaling in response to viruses and other pathogens or tumor cells. This gene is intronless and the encoded protein is secreted. [provided by RefSeq, Aug 2013]

IFNA10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09781805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNA10	NM_002171.2 link	c.395C>T	p.Thr132Ile	missense_variant	Exon 1 of 1	ENST00000357374.2	NP_002162.1	P01566A0A7R8C2Z1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNA10	ENST00000357374.2 link	c.395C>T	p.Thr132Ile	missense_variant	Exon 1 of 1	6	NM_002171.2	ENSP00000369566.1		P01566

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727184

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.395C>T (p.T132I) alteration is located in exon 1 (coding exon 1) of the IFNA10 gene. This alteration results from a C to T substitution at nucleotide position 395, causing the threonine (T) at amino acid position 132 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.3

DANN

Benign

0.92

DEOGEN2

Benign

0.0097

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.37

M_CAP

Benign

0.0035

MetaRNN

Benign

0.098

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.059

Sift

Benign

0.063

Sift4G

Benign

0.38

Polyphen

0.016

Vest4

0.065

MutPred

0.44

Loss of relative solvent accessibility (P = 0.0404);

MVP

0.26

MPC

0.22

ClinPred

0.16

GERP RS

1.8

Varity_R

0.10

gMVP

0.071

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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