rs9326114

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

2

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]
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]

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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/exons MANE Protein UniProt
LRRC53NM_001382280.1 linkuse as main transcriptc.-26-6010A>C intron_variant ENST00000294635.5 NP_001369209.1
TNNI3KNM_015978.3 linkuse as main transcriptc.2181+137T>G intron_variant ENST00000326637.8 NP_057062.1
FPGT-TNNI3KNM_001112808.3 linkuse as main transcriptc.2484+137T>G intron_variant NP_001106279.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRC53ENST00000294635.5 linkuse as main transcriptc.-26-6010A>C intron_variant 5 NM_001382280.1 ENSP00000294635 P1
TNNI3KENST00000326637.8 linkuse as main transcriptc.2181+137T>G intron_variant 1 NM_015978.3 ENSP00000322251 P1Q59H18-2

Frequencies

GnomAD3 genomes
AF:
0.0911
AC:
13859
AN:
152108
Hom.:
1573
Cov.:
32
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.:
32
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
Benign, criteria provided, single submitterclinical testingGeneDxMay 17, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

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.

Other links and lift over

dbSNP: rs9326114; hg19: chr1-74955069; COSMIC: COSV53949718; API