chr6-31572931-C-A

Position:

• chr6-31572931-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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]

LTA (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=0.11697522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTA	NM_000595.4	c.103C>A	p.Leu35Ile	missense_variant	3/4	ENST00000418386.3	NP_000586.2
LTA	NM_001159740.2	c.103C>A	p.Leu35Ile	missense_variant	3/4		NP_001153212.1
LTA	XM_047418773.1	c.103C>A	p.Leu35Ile	missense_variant	5/6		XP_047274729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTA	ENST00000418386.3	c.103C>A	p.Leu35Ile	missense_variant	3/4	1	NM_000595.4	ENSP00000413450.2
LTA	ENST00000454783.5	c.103C>A	p.Leu35Ile	missense_variant	3/4	2		ENSP00000403495.1
LTA	ENST00000471842.1	n.351C>A		non_coding_transcript_exon_variant	2/3	2
LTA	ENST00000489638.5	n.231C>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 29

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

Mar 31, 2024

The c.103C>A (p.L35I) alteration is located in exon 3 (coding exon 2) of the LTA gene. This alteration results from a C to A substitution at nucleotide position 103, causing the leucine (L) at amino acid position 35 to be replaced by an isoleucine (I). 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	0.086
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.21	T;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;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.47	N;N
REVEL	Benign	0.035
Sift	Benign	0.21	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.58	P;P
Vest4		0.16
MutPred		0.38		Gain of loop (P = 0.0502);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

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: chr6-31540708;