dbSNP rs9326114: LRRC53:c.-26-6010A>C (chr1-74489385-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001382280.1(LRRC53):c.-26-6010A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 814,438 control chromosomes in the GnomAD database, including 2,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 1587 hom., cov: 32)

Exomes 𝑓: 0.023 ( 922 hom. )

Consequence

LRRC53
NM_001382280.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.190

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:42952): (FPGT-TNNI3K readthrough) Enables protein C-terminus binding activity; protein kinase activity; and troponin I binding activity. Involved in protein phosphorylation and regulation of heart contraction. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FPGT-TNNI3K links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-74489385-T-G is Benign according to our data. Variant chr1-74489385-T-G is described in ClinVar as [Benign]. Clinvar id is 1290479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC53	NM_001382280.1 link	c.-26-6010A>C		intron_variant	Intron 1 of 4	ENST00000294635.5	NP_001369209.1
TNNI3K	NM_015978.3 link	c.2181+137T>G		intron_variant	Intron 22 of 24	ENST00000326637.8	NP_057062.1	Q59H18-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRRC53	ENST00000294635.5 link	c.-26-6010A>C	intron_variant	Intron 1 of 4	5	NM_001382280.1	ENSP00000294635.4	A6NM62
TNNI3K	ENST00000326637.8 link	c.2181+137T>G	intron_variant	Intron 22 of 24	1	NM_015978.3	ENSP00000322251.3	Q59H18-2
FPGT-TNNI3K	ENST00000557284.7 link	c.2484+137T>G	intron_variant	Intron 24 of 26	2		ENSP00000450895.3	V9GXZ4
FPGT-TNNI3K	ENST00000648585.1 link	n.*2087+137T>G	intron_variant	Intron 27 of 29			ENSP00000497631.1	A0A3B3ITB1

Frequencies

GnomAD3 genomes

AF:

0.0911

AC:

13859

AN:

152108

Hom.:

1573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0469

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.0422

Gnomad SAS

AF:

0.0646

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.0799

GnomAD4 exome

AF:

0.0230

AC:

15215

AN:

662212

Hom.:

922

AF XY:

0.0232

AC XY:

7828

AN XY:

337178

show subpopulations

Gnomad4 AFR exome

AF:

0.291

Gnomad4 AMR exome

AF:

0.0407

Gnomad4 ASJ exome

AF:

0.0218

Gnomad4 EAS exome

AF:

0.0396

Gnomad4 SAS exome

AF:

0.0560

Gnomad4 FIN exome

AF:

0.0225

Gnomad4 NFE exome

AF:

0.00920

Gnomad4 OTH exome

AF:

0.0390

GnomAD4 genome

AF:

0.0914

AC:

13915

AN:

152226

Hom.:

1587

Cov.:

AF XY:

0.0901

AC XY:

6707

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.275

Gnomad4 AMR

AF:

0.0467

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.0423

Gnomad4 SAS

AF:

0.0651

Gnomad4 FIN

AF:

0.0245

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.0795

Alfa

AF:

0.0680

Hom.:

176

Bravo

AF:

0.101

Asia WGS

AF:

0.0870

AC:

304

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 17, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.3

DANN

Benign

0.78

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