Genetic Variant LTAP1:p.Ile64Thr (chr1-154214552-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001098616.3(LTAP1):c.191T>C(p.Ile64Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,612,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

LTAP1
NM_001098616.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

Publications

3 publications found

Variant links:

Genes affected

LTAP1 (HGNC:29876): (chromosome 1 open reading frame 43) Involved in phagocytosis. Located in Golgi apparatus and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

LTAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.11056295).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTAP1	NM_001098616.3	MANE Select	c.191T>C	p.Ile64Thr	missense	Exon 3 of 7	NP_001092086.1	Q9BWL3-1
LTAP1	NM_001297720.2		c.191T>C	p.Ile64Thr	missense	Exon 3 of 6	NP_001284649.1	X6R6S3
LTAP1	NM_015449.4		c.89T>C	p.Ile30Thr	missense	Exon 2 of 6	NP_056264.1	Q9BWL3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1orf43	ENST00000368521.10	TSL:1 MANE Select	c.191T>C	p.Ile64Thr	missense	Exon 3 of 7	ENSP00000357507.4	Q9BWL3-1
C1orf43	ENST00000350592.7	TSL:1	c.89T>C	p.Ile30Thr	missense	Exon 2 of 6	ENSP00000271925.5	Q9BWL3-2
C1orf43	ENST00000362076.8	TSL:1	c.89T>C	p.Ile30Thr	missense	Exon 2 of 5	ENSP00000354496.4	Q9BWL3-4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000318

AC:

AN:

251210

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1460408

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726594

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33446

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86158

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1110804

Other (OTH)

AF:

0.0000331

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000329

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000909

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0093

Eigen

Benign

-0.091

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.74

M_CAP

Benign

0.0028

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

PhyloP100

1.8

PROVEAN

Benign

0.36

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

0.97

Polyphen

0.0

Vest4

0.23

MVP

0.22

MPC

0.43

ClinPred

0.089

GERP RS

5.9

Varity_R

0.046

gMVP

0.41

Mutation Taster

=64/36

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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