Variant 1-74475689-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001382280.1(LRRC53):c.1026T>C(p.Ala342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 713,948 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 5 hom. )

Consequence

LRRC53
NM_001382280.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

LRRC53 (HGNC:25255): (leucine rich repeat containing 53) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC53 links:

TNNI3K (HGNC:19661): (TNNI3 interacting kinase) This gene encodes a protein that belongs to the MAP kinase kinase kinase (MAPKKK) family of protein kinases. The protein contains ankyrin repeat, protein kinase and serine-rich domains and is thought to play a role in cardiac physiology. [provided by RefSeq, Sep 2012]

TNNI3K links:

FPGT-TNNI3K (HGNC:):

FPGT-TNNI3K links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 1-74475689-A-G is Benign according to our data. Variant chr1-74475689-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1694518.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-74475689-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.02 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC53	NM_001382280.1 linkuse as main transcript	c.1026T>C	p.Ala342=	synonymous_variant	4/5	ENST00000294635.5	NP_001369209.1
TNNI3K	NM_015978.3 linkuse as main transcript	c.2121+12139A>G		intron_variant		ENST00000326637.8	NP_057062.1
FPGT-TNNI3K	NM_001112808.3 linkuse as main transcript	c.2424+12139A>G		intron_variant			NP_001106279.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC53	ENST00000294635.5 linkuse as main transcript	c.1026T>C	p.Ala342=	synonymous_variant	4/5	5	NM_001382280.1	ENSP00000294635	P1
TNNI3K	ENST00000326637.8 linkuse as main transcript	c.2121+12139A>G		intron_variant		1	NM_015978.3	ENSP00000322251	P1	Q59H18-2

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

363

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000853

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00397

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00219

AC:

321

AN:

146780

Hom.:

AF XY:

0.00209

AC XY:

165

AN XY:

79036

show subpopulations

Gnomad AFR exome

AF:

0.000895

Gnomad AMR exome

AF:

0.00129

Gnomad ASJ exome

AF:

0.00172

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000451

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00445

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.00293

AC:

1645

AN:

561744

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

882

AN XY:

303034

show subpopulations

Gnomad4 AFR exome

AF:

0.000837

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.00202

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000224

Gnomad4 FIN exome

AF:

0.00184

Gnomad4 NFE exome

AF:

0.00437

Gnomad4 OTH exome

AF:

0.00229

GnomAD4 genome

AF:

0.00238

AC:

363

AN:

152204

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00397

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00352

Hom.:

Bravo

AF:

0.00230

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

LRRC53: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.5

DANN

Benign

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