Genetic Variant LRIT2:p.Gln348Pro (chr10-84222530-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001017924.5(LRIT2):c.1043A>C(p.Gln348Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

LRIT2
NM_001017924.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.390

Variant links:

Genes affected

LRIT2 (HGNC:23443): (leucine rich repeat, Ig-like and transmembrane domains 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRIT2 links:

Genome browser will be placed here

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=0.068810105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRIT2	NM_001017924.5 link	c.1043A>C	p.Gln348Pro	missense_variant	Exon 3 of 3	ENST00000372113.7	NP_001017924.1	A6NDA9-1
LRIT2	NM_001284223.1 link	c.1073A>C	p.Gln358Pro	missense_variant	Exon 4 of 4		NP_001271152.1	A6NDA9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRIT2	ENST00000372113.7 link	c.1043A>C	p.Gln348Pro	missense_variant	Exon 3 of 3	1	NM_001017924.5	ENSP00000361185.3		A6NDA9-1
LRIT2	ENST00000538192.5 link	c.1073A>C	p.Gln358Pro	missense_variant	Exon 4 of 4	1		ENSP00000438264.1		A6NDA9-2

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251394

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000823

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1043A>C (p.Q348P) alteration is located in exon 3 (coding exon 3) of the LRIT2 gene. This alteration results from a A to C substitution at nucleotide position 1043, causing the glutamine (Q) at amino acid position 348 to be replaced by a proline (P). 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

0.059

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.43

CADD

Benign

4.0

DANN

Benign

0.54

DEOGEN2

Benign

0.0019

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;L

PrimateAI

Benign

0.29

PROVEAN

Benign

0.60

N;N

REVEL

Benign

0.042

Sift

Benign

0.21

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.0070

.;B

Vest4

0.12

MVP

0.12

MPC

0.0049

ClinPred

0.024

GERP RS

-1.6

Varity_R

0.071

gMVP

0.41

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