12-6384661-T-A

Variant names:

• chr12-6384661-T-A
• NM_002342.3:c.170T>A

Variant summary

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

The NM_002342.3(LTBR):​c.170T>A​(p.Ile57Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LTBR NM_002342.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.192

Genes affected

LTBR (HGNC:6718): (lymphotoxin beta receptor) This gene encodes a member of the tumor necrosis factor receptor superfamily. The major ligands of this receptor include lymphotoxin alpha/beta and tumor necrosis factor ligand superfamily member 14. The encoded protein plays a role in signalling during the development of lymphoid and other organs, lipid metabolism, immune response, and programmed cell death. Activity of this receptor has also been linked to carcinogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBR	NM_002342.3	c.170T>A	p.Ile57Asn	missense_variant	Exon 2 of 10	ENST00000228918.9	NP_002333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBR	ENST00000228918.9	c.170T>A	p.Ile57Asn	missense_variant	Exon 2 of 10	1	NM_002342.3	ENSP00000228918.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.170T>A (p.I57N) alteration is located in exon 2 (coding exon 2) of the LTBR gene. This alteration results from a T to A substitution at nucleotide position 170, causing the isoleucine (I) at amino acid position 57 to be replaced by an asparagine (N). 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	0.30
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	.;T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Pathogenic	0.48	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.83	.;P;.
Vest4		0.27
MutPred		0.49		.;Gain of disorder (P = 0.0355);Gain of disorder (P = 0.0355);
MVP		0.53
MPC		2.5
ClinPred		0.87	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.79

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: chr12-6493827;