Variant 12-54632334-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000257867.5(LACRT):c.160C>G(p.Pro54Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LACRT
ENST00000257867.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.286

Variant links:

Genes affected

LACRT (HGNC:16430): (lacritin) The protein encoded by this gene is highly expressed in the lacrimal glands and localized primarily to secretory granules and secretory fluid. It augments lacrimal acinar cell secretion, promotes ductal cell proliferation, and stimulates signaling through tyrosine phosphorylation and release of calcium. [provided by RefSeq, Jul 2008]

LACRT links:

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ACMG classification

Classification made for transcript

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=0.069961965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACRT	NM_033277.2 linkuse as main transcript	c.160C>G	p.Pro54Ala	missense_variant	3/5	ENST00000257867.5	NP_150593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LACRT	ENST00000257867.5 linkuse as main transcript	c.160C>G	p.Pro54Ala	missense_variant	3/5	1	NM_033277.2	ENSP00000257867	P2
LACRT	ENST00000547511.5 linkuse as main transcript	c.160C>G	p.Pro54Ala	missense_variant	3/5	3		ENSP00000447536	A2
LACRT	ENST00000546721.5 linkuse as main transcript	c.70C>G	p.Pro24Ala	missense_variant	2/4	5		ENSP00000448193
LACRT	ENST00000549816.1 linkuse as main transcript	n.206C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251290

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.160C>G (p.P54A) alteration is located in exon 3 (coding exon 3) of the LACRT gene. This alteration results from a C to G substitution at nucleotide position 160, causing the proline (P) at amino acid position 54 to be replaced by an alanine (A). 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

0.054

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.4

DANN

Benign

0.95

DEOGEN2

Benign

0.068

T;.;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.48

T;T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Benign

0.077

Sift

Benign

0.093

T;.;.

Sift4G

Benign

0.22

T;T;T

Polyphen

0.020

.;.;B

Vest4

0.11, 0.085

MutPred

0.13

.;Loss of glycosylation at P54 (P = 0.0194);Loss of glycosylation at P54 (P = 0.0194);

MVP

0.061

MPC

0.035

ClinPred

0.033

GERP RS

2.4

Varity_R

0.47

gMVP

0.022

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over