1-100159391-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_144620.4(LRRC39):c.244C>T(p.Leu82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00973 in 1,608,540 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (6 hom., cov: 32)
  • Exomes 𝑓: 0.010 (85 hom.)
• Consequence: LRRC39 NM_144620.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

Genes affected

LRRC39 (HGNC:28228): (leucine rich repeat containing 39) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Predicted to be located in M band. Predicted to be active in cytoplasm and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 1-100159391-G-A is Benign according to our data. Variant chr1-100159391-G-A is described in ClinVar as [Benign]. Clinvar id is 776338.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.21 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC39	NM_144620.4	c.244C>T	p.Leu82=	synonymous_variant	5/10	ENST00000370137.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC39	ENST00000370137.6	c.244C>T	p.Leu82=	synonymous_variant	5/10	1	NM_144620.4	P1
LRRC39	ENST00000370138.1	c.244C>T	p.Leu82=	synonymous_variant	5/11	5
LRRC39	ENST00000342895.8	c.244C>T	p.Leu82=	synonymous_variant	5/10	5		P1

Frequencies

GnomAD3 genomes AF: 0.00643 AC: 978 AN: 152154 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00605

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00713 AC: 1762 AN: 247114 Hom.: 18 AF XY: 0.00719 AC XY: 962 AN XY: 133714

Gnomad AFR exome AF: 0.00213

Gnomad AMR exome AF: 0.00187

Gnomad ASJ exome AF: 0.00798

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00128

Gnomad FIN exome AF: 0.00722

Gnomad NFE exome AF: 0.0120

Gnomad OTH exome AF: 0.00670

GnomAD4 exome AF: 0.0101 AC: 14676 AN: 1456268 Hom.: 85 Cov.: 30 AF XY: 0.0101 AC XY: 7289 AN XY: 724408

Gnomad4 AFR exome AF: 0.00142

Gnomad4 AMR exome AF: 0.00166

Gnomad4 ASJ exome AF: 0.00699

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00158

Gnomad4 FIN exome AF: 0.00806

Gnomad4 NFE exome AF: 0.0120

Gnomad4 OTH exome AF: 0.00738

GnomAD4 genome AF: 0.00642 AC: 978 AN: 152272 Hom.: 6 Cov.: 32 AF XY: 0.00580 AC XY: 432 AN XY: 74448

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00605

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00756 Hom.: 0

Bravo AF: 0.00590

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	5.2
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs80221535; hg19: chr1-100624947;