chr6-31572931-C-A

Variant names:

• chr6-31572931-C-A
• NM_000595.4:c.103C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000595.4(LTA):​c.103C>A​(p.Leu35Ile) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: LTA NM_000595.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0700
• Publications: 0 publications found

Genes affected

LTA (HGNC:6709): (lymphotoxin alpha) The encoded protein, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The protein is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchor lymphotoxin-alpha to the cell surface. This protein also mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis. Genetic variations in this gene are associated with susceptibility to leprosy type 4, myocardial infarction, non-Hodgkin's lymphoma, and psoriatic arthritis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

ENSG00000289406 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11697522).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000595.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA	NM_000595.4	MANE Select	c.103C>A	p.Leu35Ile	missense	Exon 3 of 4	NP_000586.2
	LTA	NM_001159740.2		c.103C>A	p.Leu35Ile	missense	Exon 3 of 4	NP_001153212.1	Q5STV3
	LOC100287329	NR_149045.1		n.-228G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA	ENST00000418386.3	TSL:1 MANE Select	c.103C>A	p.Leu35Ile	missense	Exon 3 of 4	ENSP00000413450.2	P01374
	LTA	ENST00000454783.5	TSL:2	c.103C>A	p.Leu35Ile	missense	Exon 3 of 4	ENSP00000403495.1	P01374
	LTA	ENST00000877327.1		c.103C>A	p.Leu35Ile	missense	Exon 2 of 3	ENSP00000547386.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 29

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.34	N
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.070
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.035
Sift	Benign	0.21	T
Sift4G	Benign	0.44	T
Polyphen		0.58	P
Vest4		0.16
MutPred		0.38		Gain of loop (P = 0.0502)
MVP		0.32
MPC		1.2
ClinPred		0.15	T
GERP RS		2.1
Varity_R		0.033
gMVP		0.44
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

hg19: chr6-31540708;