rs1730493375

Variant names:

• chr3-197791502-G-A
• rs1730493375
• NM_001365715.1:c.224G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-197791502-G-A
• chr3-197791502-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365715.1(LRCH3):​c.224G>A​(p.Gly75Glu) 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. 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: 3.19
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24875617).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365715.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRCH3	NM_001365715.1	MANE Select	c.224G>A	p.Gly75Glu	missense	Exon 1 of 21	NP_001352644.1	Q96II8-1
	LRCH3	NM_001363887.1		c.224G>A	p.Gly75Glu	missense	Exon 1 of 21	NP_001350816.1	Q96II8-2
	LRCH3	NM_001365716.1		c.224G>A	p.Gly75Glu	missense	Exon 1 of 20	NP_001352645.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRCH3	ENST00000425562.7	TSL:5 MANE Select	c.224G>A	p.Gly75Glu	missense	Exon 1 of 21	ENSP00000393579.2	Q96II8-1
	LRCH3	ENST00000334859.8	TSL:1	c.224G>A	p.Gly75Glu	missense	Exon 1 of 19	ENSP00000334375.4	Q96II8-3
	LRCH3	ENST00000428136.2	TSL:5	c.224G>A	p.Gly75Glu	missense	Exon 1 of 21	ENSP00000394763.2	Q96II8-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.078
Eigen_PC	Benign	0.018
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.055
Sift	Benign	0.046	D
Sift4G	Uncertain	0.038	D
Polyphen		0.83	P
Vest4		0.40
MutPred		0.36		Loss of MoRF binding (P = 0.0567)
MVP		0.45
MPC		0.14
ClinPred		0.87	D
GERP RS		2.8
PromoterAI		0.0010	Neutral
Varity_R		0.46
gMVP		0.36
Mutation Taster		=88/12	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: rs1730493375; hg19: chr3-197518373;