NM_000595.4:c.179C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000595.4(LTA):c.179C>A(p.Thr60Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,611,200 control chromosomes in the GnomAD database, including 103,451 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T60A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.38 ( 11465 hom., cov: 28)

Exomes 𝑓: 0.35 ( 91986 hom. )

Consequence

LTA
NM_000595.4 missense

Scores

Clinical Significance

Benign; risk factor no assertion criteria provided B:1O:1

Conservation

PhyloP100: 0.741

Publications

257 publications found

Variant links:

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 links:

ENSG00000289406 (HGNC:):

ENSG00000289406 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.4083595E-4).

BP6

Variant 6-31573007-C-A is Benign according to our data. Variant chr6-31573007-C-A is described in ClinVar as Benign|risk_factor. ClinVar VariationId is 14379.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA	NM_000595.4	MANE Select	c.179C>A	p.Thr60Asn	missense	Exon 3 of 4	NP_000586.2
	LTA	NM_001159740.2		c.179C>A	p.Thr60Asn	missense	Exon 3 of 4	NP_001153212.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LTA	ENST00000418386.3	TSL:1 MANE Select	c.179C>A	p.Thr60Asn	missense	Exon 3 of 4	ENSP00000413450.2
LTA	ENST00000454783.5	TSL:2	c.179C>A	p.Thr60Asn	missense	Exon 3 of 4	ENSP00000403495.1
LTA	ENST00000877327.1		c.179C>A	p.Thr60Asn	missense	Exon 2 of 3	ENSP00000547386.1

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57634

AN:

151122

Hom.:

11454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.502

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.350

GnomAD2 exomes

AF:

0.347

AC:

85595

AN:

246840

AF XY:

0.339

show subpopulations

Gnomad AFR exome

AF:

0.501

Gnomad AMR exome

AF:

0.338

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.498

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.351

AC:

512722

AN:

1459960

Hom.:

91986

Cov.:

AF XY:

0.348

AC XY:

252459

AN XY:

726340

show subpopulations

African (AFR)

AF:

0.508

AC:

17003

AN:

33460

American (AMR)

AF:

0.336

AC:

14993

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

6524

AN:

26128

East Asian (EAS)

AF:

0.434

AC:

17213

AN:

39694

South Asian (SAS)

AF:

0.284

AC:

24521

AN:

86238

European-Finnish (FIN)

AF:

0.313

AC:

16388

AN:

52316

Middle Eastern (MID)

AF:

0.346

AC:

1998

AN:

5768

European-Non Finnish (NFE)

AF:

0.353

AC:

392842

AN:

1111304

Other (OTH)

AF:

0.352

AC:

21240

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

17885

35771

53656

71542

89427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12788

25576

38364

51152

63940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.381

AC:

57687

AN:

151240

Hom.:

11465

Cov.:

AF XY:

0.377

AC XY:

27836

AN XY:

73858

show subpopulations

African (AFR)

AF:

0.502

AC:

20649

AN:

41150

American (AMR)

AF:

0.346

AC:

5258

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

837

AN:

3468

East Asian (EAS)

AF:

0.471

AC:

2382

AN:

5060

South Asian (SAS)

AF:

0.277

AC:

1331

AN:

4806

European-Finnish (FIN)

AF:

0.298

AC:

3125

AN:

10476

Middle Eastern (MID)

AF:

0.318

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.339

AC:

22953

AN:

67788

Other (OTH)

AF:

0.348

AC:

727

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1663

3325

4988

6650

8313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.351

Hom.:

45322

Bravo

AF:

0.391

TwinsUK

AF:

0.375

AC:

1391

ALSPAC

AF:

0.379

AC:

1459

ESP6500AA

AF:

0.511

AC:

1543

ESP6500EA

AF:

0.331

AC:

1793

ExAC

AF:

0.347

AC:

41204

Asia WGS

AF:

0.329

AC:

1145

AN:

3478

EpiCase

AF:

0.318

EpiControl

AF:

0.322

ClinVar

ClinVar submissions as Germline

Significance:Benign; risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

LTA-related disorder (1)

Myocardial infarction, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.17

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.42

MetaRNN

Benign

0.00044

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

0.74

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.010

REVEL

Benign

0.025

Sift

Benign

0.39

Sift4G

Uncertain

0.045

Polyphen

0.0050

Vest4

0.047

MPC

1.1

ClinPred

0.0010

GERP RS

3.1

Varity_R

0.030

gMVP

0.30

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over