6-43508834-A-C

Variant names:

• chr6-43508834-A-C
• NM_001012974.4:c.359T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001012974.4(LRRC73):​c.359T>G​(p.Leu120Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC73 NM_001012974.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.30
• Publications: 0 publications found

Genes affected

LRRC73 (HGNC:21375): (leucine rich repeat containing 73)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC73	NM_001012974.4	c.359T>G	p.Leu120Arg	missense_variant	Exon 2 of 6	ENST00000372441.2	NP_001012992.1
LRRC73	NM_001271882.2	c.-11T>G		5_prime_UTR_variant	Exon 2 of 6		NP_001258811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC73	ENST00000372441.2	c.359T>G	p.Leu120Arg	missense_variant	Exon 2 of 6	1	NM_001012974.4	ENSP00000361518.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.359T>G (p.L120R) alteration is located in exon 2 (coding exon 2) of the LRRC73 gene. This alteration results from a T to G substitution at nucleotide position 359, causing the leucine (L) at amino acid position 120 to be replaced by an arginine (R). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.5	M
PhyloP100		8.3
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Pathogenic	0.88
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.73		Gain of methylation at L120 (P = 0.0669);
MVP		0.88
MPC		2.1
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.86
gMVP		0.96
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

hg19: chr6-43476572;