rs4280262

Variant names:

• chr16-11553636-T-A
• NM_001136472.2:c.274A>T

Your query was ambiguous. Multiple possible variants found:

• chr16-11553636-T-A
• chr16-11553636-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001136472.2(LITAF):​c.274A>T​(p.Ile92Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I92V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LITAF NM_001136472.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

Genes affected

LITAF (HGNC:16841): (lipopolysaccharide induced TNF factor) Lipopolysaccharide is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor-alpha (TNF-alpha) and other inflammatory mediators. This gene encodes lipopolysaccharide-induced TNF-alpha factor, which is a DNA-binding protein and can mediate the TNF-alpha expression by direct binding to the promoter region of the TNF-alpha gene. The transcription of this gene is induced by tumor suppressor p53 and has been implicated in the p53-induced apoptotic pathway. Mutations in this gene cause Charcot-Marie-Tooth disease type 1C (CMT1C) and may be involved in the carcinogenesis of extramammary Paget's disease (EMPD). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a domain LITAF (size 84) in uniprot entity LITAF_HUMAN there are 9 pathogenic changes around while only 0 benign (100%) in NM_001136472.2
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LITAF	NM_001136472.2	c.274A>T	p.Ile92Phe	missense_variant	Exon 3 of 4	ENST00000622633.5	NP_001129944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LITAF	ENST00000622633.5	c.274A>T	p.Ile92Phe	missense_variant	Exon 3 of 4	1	NM_001136472.2	ENSP00000483114.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461810 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727198

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	12
DANN	Benign	0.79
DEOGEN2	Pathogenic	0.88	D;D;.;D;.;D;D;D;D;.;.;.;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.65	.;T;.;.;T;.;.;.;T;T;T;T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.72	D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.3	L;L;L;L;L;L;L;L;.;.;L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.7	.;.;D;D;D;.;.;.;.;.;.;.;.
REVEL	Uncertain	0.44
Sift	Uncertain	0.0040	.;.;D;D;D;.;.;.;.;.;.;.;.
Sift4G	Uncertain	0.039	D;D;D;D;D;D;D;D;.;.;D;.;D
Polyphen		0.43	B;B;.;B;.;B;B;B;.;.;.;.;.
Vest4		0.32
MutPred		0.46		Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);Gain of catalytic residue at I92 (P = 0.034);
MVP		0.97
MPC		0.25
ClinPred		0.82	D
GERP RS		1.1
Varity_R		0.15
gMVP		0.75

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: chr16-11647492;