rs151080979

chr12-69610255-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_201550.4(LRRC10):c.584T>C(p.Ile195Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,614,190 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (29 hom.)
• Consequence: LRRC10 NM_201550.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 9.25

Genes affected

LRRC10 (HGNC:20264): (leucine rich repeat containing 10) Predicted to enable actin binding activity. Predicted to be involved in cardiac muscle cell development. Predicted to be located in myofibril. Predicted to be active in cytoskeleton and sarcomere. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012428105).
• BP6: Variant 12-69610255-A-G is Benign according to our data. Variant chr12-69610255-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 478141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC10	NM_201550.4	c.584T>C	p.Ile195Thr	missense_variant	1/1	ENST00000361484.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC10	ENST00000361484.5	c.584T>C	p.Ile195Thr	missense_variant	1/1		NM_201550.4	P1

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 596 AN: 152198 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00551

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00491 AC: 1234 AN: 251418 Hom.: 5 AF XY: 0.00498 AC XY: 677 AN XY: 135888

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00477

Gnomad FIN exome AF: 0.00948

Gnomad NFE exome AF: 0.00656

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00569 AC: 8311 AN: 1461874 Hom.: 29 Cov.: 31 AF XY: 0.00568 AC XY: 4130 AN XY: 727236

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00219

Gnomad4 ASJ exome AF: 0.000536

Gnomad4 EAS exome AF: 0.000605

Gnomad4 SAS exome AF: 0.00458

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.00614

Gnomad4 OTH exome AF: 0.00570

GnomAD4 genome AF: 0.00390 AC: 594 AN: 152316 Hom.: 1 Cov.: 33 AF XY: 0.00438 AC XY: 326 AN XY: 74490

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.00551

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00464 Hom.: 4

Bravo AF: 0.00275

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00628 AC: 54

ExAC AF: 0.00558 AC: 678

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00458

EpiControl AF: 0.00533

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	LRRC10: BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 14, 2019	This variant is associated with the following publications: (PMID: 29431102) -

Dilated Cardiomyopathy, Dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.020
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.78
MVP		0.41
MPC		0.76
ClinPred		0.018	T
GERP RS		5.6
Varity_R		0.52
gMVP		0.63

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: rs151080979; hg19: chr12-70004035; COSMIC: COSV100825459;