6-31580924-T-G

Position:

• chr6-31580924-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002341.2(LTB):​c.520A>C​(p.Thr174Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LTB NM_002341.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.18

Genes affected

LTB (HGNC:6711): (lymphotoxin beta) Lymphotoxin beta is a type II membrane protein of the TNF family. It anchors lymphotoxin-alpha to the cell surface through heterotrimer formation. The predominant form on the lymphocyte surface is the lymphotoxin-alpha 1/beta 2 complex (e.g. 1 molecule alpha/2 molecules beta) and this complex is the primary ligand for the lymphotoxin-beta receptor. The minor complex is lymphotoxin-alpha 2/beta 1. LTB is an inducer of the inflammatory response system and involved in normal development of lymphoid tissue. Lymphotoxin-beta isoform b is unable to complex with lymphotoxin-alpha suggesting a function for lymphotoxin-beta which is independent of lympyhotoxin-alpha. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

LTB (HGNC:):

ACMG classification

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=0.1350748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTB	NM_002341.2	c.520A>C	p.Thr174Pro	missense_variant	4/4	ENST00000429299.3	NP_002332.1
LTB	NM_009588.1	c.*240A>C		3_prime_UTR_variant	3/3		NP_033666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTB	ENST00000429299.3	c.520A>C	p.Thr174Pro	missense_variant	4/4	1	NM_002341.2	ENSP00000410481.3
LTB	ENST00000446745.2	c.*240A>C		3_prime_UTR_variant	3/3	1		ENSP00000416113.2
LTB	ENST00000482429.1	n.1088A>C		non_coding_transcript_exon_variant	2/2	2
LTB	ENST00000483972.1	n.339A>C		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 17, 2024

The c.520A>C (p.T174P) alteration is located in exon 4 (coding exon 4) of the LTB gene. This alteration results from a A to C substitution at nucleotide position 520, causing the threonine (T) at amino acid position 174 to be replaced by a proline (P). 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	0.085
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	7.4
DANN	Benign	0.90
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.24
Sift	Benign	0.21	T
Sift4G	Benign	0.22	T
Polyphen		0.14	B
Vest4		0.17
MutPred		0.54		Loss of phosphorylation at T174 (P = 0.0091);
MVP		0.46
MPC		2.1
ClinPred		0.17	T
GERP RS		-3.2
Varity_R		0.30
gMVP		0.58

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: chr6-31548701;