NM_001365715.1:c.109G>A

Variant names:

• chr3-197791387-G-A
• NM_001365715.1:c.109G>A

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.109G>A​(p.Gly37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRCH3 NM_001365715.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.275
• 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=0.12772754).

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.109G>A	p.Gly37Ser	missense	Exon 1 of 21	NP_001352644.1	Q96II8-1
	LRCH3	NM_001363887.1		c.109G>A	p.Gly37Ser	missense	Exon 1 of 21	NP_001350816.1	Q96II8-2
	LRCH3	NM_001365716.1		c.109G>A	p.Gly37Ser	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.109G>A	p.Gly37Ser	missense	Exon 1 of 21	ENSP00000393579.2	Q96II8-1
	LRCH3	ENST00000334859.8	TSL:1	c.109G>A	p.Gly37Ser	missense	Exon 1 of 19	ENSP00000334375.4	Q96II8-3
	LRCH3	ENST00000428136.2	TSL:5	c.109G>A	p.Gly37Ser	missense	Exon 1 of 21	ENSP00000394763.2	Q96II8-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444666 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717308

African (AFR) AF: 0.00 AC: 0 AN: 32978

American (AMR) AF: 0.00 AC: 0 AN: 41352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25666

East Asian (EAS) AF: 0.00 AC: 0 AN: 38918

South Asian (SAS) AF: 0.00 AC: 0 AN: 83670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105370

Other (OTH) AF: 0.00 AC: 0 AN: 59780

GnomAD4 genome Cov.: 31

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	Benign	0.083
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.28
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.016
Sift	Benign	0.12	T
Sift4G	Benign	0.46	T
Polyphen		0.063	B
Vest4		0.27
MutPred		0.28		Gain of glycosylation at G37 (P = 0.0019)
MVP		0.52
MPC		0.12
ClinPred		0.28	T
GERP RS		4.3
PromoterAI		-0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.40
Mutation Taster		=81/19	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: chr3-197518258;