16-11553684-C-G

Variant names:

• chr16-11553684-C-G
• NM_001136472.2:c.226G>C

Variant summary

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

The NM_001136472.2(LITAF):​c.226G>C​(p.Val76Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: LITAF NM_001136472.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.69

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.226G>C	p.Val76Leu	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.226G>C	p.Val76Leu	missense_variant	Exon 3 of 4	1	NM_001136472.2	ENSP00000483114.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461782 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727182

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;T;.;T;.;T;T;T;T;.;.;.;.
Eigen	Benign	0.082
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	.;T;.;.;D;.;.;.;T;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.71	D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.095	D
MutationAssessor	Benign	2.0	M;M;M;M;M;M;M;M;.;.;M;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.5	.;.;N;N;N;.;.;.;.;.;.;.;.
REVEL	Uncertain	0.55
Sift	Uncertain	0.022	.;.;D;T;D;.;.;.;.;.;.;.;.
Sift4G	Uncertain	0.029	D;D;T;D;T;D;D;D;.;.;T;.;T
Polyphen		0.41	B;B;.;B;.;B;B;B;.;.;.;.;.
Vest4		0.71
MutPred		0.67		Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);Loss of glycosylation at T75 (P = 0.0916);
MVP		0.93
MPC		0.27
ClinPred		0.84	D
GERP RS		4.4
Varity_R		0.11
gMVP		0.68

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: chr16-11647540;