chr6-31581079-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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A122V) has been classified as Benign.

• 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;