rs596204

Positions:

• chr1-74470690-A-C
• chr1-74470690-A-G
• chr1-74470690-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001382280.1(LRRC53):​c.2932T>G​(p.Ser978Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LRRC53 NM_001382280.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089301705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC53	NM_001382280.1	c.2932T>G	p.Ser978Ala	missense_variant	5/5	ENST00000294635.5
TNNI3K	NM_015978.3	c.2121+7140A>C		intron_variant		ENST00000326637.8
FPGT-TNNI3K	NM_001112808.3	c.2424+7140A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC53	ENST00000294635.5	c.2932T>G	p.Ser978Ala	missense_variant	5/5	5	NM_001382280.1	P1
TNNI3K	ENST00000326637.8	c.2121+7140A>C		intron_variant		1	NM_015978.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.44
DANN	Benign	0.65
DEOGEN2	Benign	0.0016	T
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.089	T
MutationTaster	Benign	1.0	P;P
Sift4G	Benign	0.62	T
Vest4		0.074
MVP		0.45
GERP RS		2.1
Varity_R		0.049
gMVP		0.00091

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: rs596204; hg19: chr1-74936374;