6-31581079-G-T

Variant names:

• chr6-31581079-G-T
• rs2229699
• NM_002341.2:c.365C>A

Variant summary

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

The NM_002341.2(LTB):​c.365C>A​(p.Ala122Asp) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LTB NM_002341.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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]

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=0.09804922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTB	NM_002341.2	c.365C>A	p.Ala122Asp	missense_variant	Exon 4 of 4	ENST00000429299.3	NP_002332.1
LTB	NM_009588.1	c.*85C>A		3_prime_UTR_variant	Exon 3 of 3		NP_033666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTB	ENST00000429299.3	c.365C>A	p.Ala122Asp	missense_variant	Exon 4 of 4	1	NM_002341.2	ENSP00000410481.3
LTB	ENST00000446745	c.*85C>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000416113.2
LTB	ENST00000482429.1	n.933C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
LTB	ENST00000483972.1	n.184C>A		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.035	N
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.20	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.028
Sift	Benign	0.27	T
Sift4G	Benign	0.43	T
Polyphen		0.0030	B
Vest4		0.17
MutPred		0.16		Gain of disorder (P = 0.0625);
MVP		0.51
MPC		1.9
ClinPred		0.25	T
GERP RS		4.5
Varity_R		0.26
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs2229699; hg19: chr6-31548856;