Variant 19-18396242-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000339007.4(LRRC25):c.722A>G(p.Asp241Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,612,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

LRRC25
ENST00000339007.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Variant links:

Genes affected

LRRC25 (HGNC:29806): (leucine rich repeat containing 25) Predicted to be located in cytoplasm. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
LRRC25	NM_145256.3 linkuse as main transcript	c.722A>G	p.Asp241Gly	missense_variant	1/2	ENST00000339007.4	NP_660299.2	Q8N386
LRRC25	XM_005259739.5 linkuse as main transcript	c.722A>G	p.Asp241Gly	missense_variant	2/3		XP_005259796.1	Q8N386

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC25	ENST00000339007.4 linkuse as main transcript	c.722A>G	p.Asp241Gly	missense_variant	1/2	1	NM_145256.3	ENSP00000340983.2		Q8N386
LRRC25	ENST00000595840.1 linkuse as main transcript	c.722A>G	p.Asp241Gly	missense_variant	2/3	1		ENSP00000472290.1		Q8N386

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

248822

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134674

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000448

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000876

AC:

128

AN:

1460454

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

726246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.000112

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Feb 23, 2023

The c.722A>G (p.D241G) alteration is located in exon 1 (coding exon 1) of the LRRC25 gene. This alteration results from a A to G substitution at nucleotide position 722, causing the aspartic acid (D) at amino acid position 241 to be replaced by a glycine (G). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.64

.;T

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.61

D;D

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

0.96

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-4.4

D;.

REVEL

Benign

0.19

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.050

T;T

Polyphen

1.0

D;D

Vest4

0.55

MutPred

0.26

Gain of glycosylation at S238 (P = 0.0721);Gain of glycosylation at S238 (P = 0.0721);

MVP

0.45

MPC

0.61

ClinPred

0.48

GERP RS

4.1

Varity_R

0.70

gMVP

0.66

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