6-43508816-C-T

Variant names:

• chr6-43508816-C-T
• rs1792581934
• NM_001012974.4:c.377G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001012974.4(LRRC73):​c.377G>A​(p.Gly126Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G126S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC73 NM_001012974.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.01
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC73	NM_001012974.4	c.377G>A	p.Gly126Asp	missense_variant	Exon 2 of 6	ENST00000372441.2	NP_001012992.1
LRRC73	NM_001271882.2	c.8G>A	p.Gly3Asp	missense_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.377G>A	p.Gly126Asp	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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.020	D
Sift4G	Benign	0.061	T
Polyphen		1.0	D
Vest4		0.89
MutPred		0.57		Gain of relative solvent accessibility (P = 0.09);
MVP		0.59
MPC		2.1
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.63
gMVP		0.91
Mutation Taster		=63/37	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

dbSNP: rs1792581934; hg19: chr6-43476554;