1-74472172-ATCT-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_001382280.1(LRRC53):c.1447_1449del(p.Arg483del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 716,972 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (3 hom.)
• Consequence: LRRC53 NM_001382280.1 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.21

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]

FPGT-TNNI3K (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001382280.1. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 1-74472172-ATCT-A is Benign according to our data. Variant chr1-74472172-ATCT-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638880.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC53	NM_001382280.1	c.1447_1449del	p.Arg483del	inframe_deletion	5/5	ENST00000294635.5
TNNI3K	NM_015978.3	c.2121+8629_2121+8631del		intron_variant		ENST00000326637.8
FPGT-TNNI3K	NM_001112808.3	c.2424+8629_2424+8631del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC53	ENST00000294635.5	c.1447_1449del	p.Arg483del	inframe_deletion	5/5	5	NM_001382280.1	P1
TNNI3K	ENST00000326637.8	c.2121+8629_2121+8631del		intron_variant		1	NM_015978.3	P1

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00160 AC: 239 AN: 149390 Hom.: 2 AF XY: 0.00153 AC XY: 123 AN XY: 80342

Gnomad AFR exome AF: 0.000147

Gnomad AMR exome AF: 0.000163

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000222

Gnomad FIN exome AF: 0.0111

Gnomad NFE exome AF: 0.000652

Gnomad OTH exome AF: 0.00162

GnomAD4 exome AF: 0.00161 AC: 907 AN: 564724 Hom.: 3 AF XY: 0.00154 AC XY: 469 AN XY: 304720

Gnomad4 AFR exome AF: 0.000127

Gnomad4 AMR exome AF: 0.000115

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000398

Gnomad4 FIN exome AF: 0.0119

Gnomad4 NFE exome AF: 0.000849

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.00135 AC: 206 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.00168 AC XY: 125 AN XY: 74446

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0108

Gnomad4 NFE AF: 0.00119

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00142 Hom.: 0

Bravo AF: 0.000397

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

LRRC53: BS2 -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs565475322; hg19: chr1-74937856;