11-319893-A-T

Variant names:

• chr11-319893-A-T
• NM_021034.3:c.347T>A

Variant summary

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

The NM_021034.3(IFITM3):​c.347T>A​(p.Leu116His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 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: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IFITM3 NM_021034.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

Genes affected

IFITM3 (HGNC:5414): (interferon induced transmembrane protein 3) Interferon-induced transmembrane (IFITM) proteins are a family of interferon induced antiviral proteins. The family contains five members, including IFITM1, IFITM2 and IFITM3 and belong to the CD225 superfamily. The protein encoded by this gene restricts cellular entry by diverse viral pathogens, such as influenza A virus, Ebola virus and Sars-CoV-2. [provided by RefSeq, Nov 2021]

ENSG00000251661 (HGNC:58185):

LOC105376505 (HGNC:):

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, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFITM3	NM_021034.3	c.347T>A	p.Leu116His	missense_variant	Exon 2 of 2	ENST00000399808.5	NP_066362.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFITM3	ENST00000399808.5	c.347T>A	p.Leu116His	missense_variant	Exon 2 of 2	1	NM_021034.3	ENSP00000382707.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Uncertain	0.79	D;D;D
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.071	T;.;T
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Uncertain	-0.094	T
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.7	D;D;.
REVEL	Uncertain	0.41
Sift	Benign	0.071	T;T;.
Sift4G	Uncertain	0.034	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.49
MutPred		0.67		Loss of stability (P = 0.0244);.;.;
MVP		0.70
MPC		1.3
ClinPred		0.68	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.24
gMVP		0.65

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: chr11-319893;