3-197791433-C-G

Variant names:

• chr3-197791433-C-G
• NM_001365715.1:c.155C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001365715.1(LRCH3):​c.155C>G​(p.Ala52Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LRCH3 NM_001365715.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25

Genes affected

LRCH3 (HGNC:28637): (leucine rich repeats and calponin homology domain containing 3) Involved in septin cytoskeleton organization. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37767464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRCH3	NM_001365715.1	c.155C>G	p.Ala52Gly	missense_variant	Exon 1 of 21	ENST00000425562.7	NP_001352644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRCH3	ENST00000425562.7	c.155C>G	p.Ala52Gly	missense_variant	Exon 1 of 21	5	NM_001365715.1	ENSP00000393579.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.155C>G (p.A52G) alteration is located in exon 1 (coding exon 1) of the LRCH3 gene. This alteration results from a C to G substitution at nucleotide position 155, causing the alanine (A) at amino acid position 52 to be replaced by a glycine (G). 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;.;.;T;.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	.;D;D;D;D;D
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.38	T;T;T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.6	M;M;M;.;M;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.4	D;.;D;D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D;.;D;D;D;D
Sift4G	Uncertain	0.010	D;.;D;D;D;D
Polyphen		0.99	D;D;.;D;P;.
Vest4		0.50
MutPred		0.30		Loss of stability (P = 0.0136);Loss of stability (P = 0.0136);Loss of stability (P = 0.0136);Loss of stability (P = 0.0136);Loss of stability (P = 0.0136);Loss of stability (P = 0.0136);
MVP		0.75
MPC		0.32
ClinPred		0.98	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.74
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-197518304;