1-100152390-C-A

Position:

• chr1-100152390-C-A

Variant summary

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

The NM_144620.4(LRRC39):​c.947G>T​(p.Arg316Ile) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC39 NM_144620.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.223

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 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=0.093607605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC39	NM_144620.4	c.947G>T	p.Arg316Ile	missense_variant	9/10	ENST00000370137.6	NP_653221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC39	ENST00000370137.6	c.947G>T	p.Arg316Ile	missense_variant	9/10	1	NM_144620.4	ENSP00000359156	P1
LRRC39	ENST00000370138.1	c.947G>T	p.Arg316Ile	missense_variant	9/11	5		ENSP00000359157
LRRC39	ENST00000342895.8	c.947G>T	p.Arg316Ile	missense_variant	9/10	5		ENSP00000344470	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2024

The c.947G>T (p.R316I) alteration is located in exon 9 (coding exon 7) of the LRRC39 gene. This alteration results from a G to T substitution at nucleotide position 947, causing the arginine (R) at amino acid position 316 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.013	.;T;T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.71	.;.;T;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.094	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M;M;M;M
MutationTaster	Benign	0.95	N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	.;N;N;N
REVEL	Benign	0.080
Sift	Uncertain	0.0010	.;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		0.0010	B;B;B;B
Vest4		0.26
MutPred		0.48		Loss of disorder (P = 0.0384);Loss of disorder (P = 0.0384);Loss of disorder (P = 0.0384);Loss of disorder (P = 0.0384);
MVP		0.31
MPC		0.15
ClinPred		0.30	T
GERP RS		-2.8
Varity_R		0.11
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-100617946;