rs1383657282

Variant names:

• chr3-197791454-C-A
• NM_001365715.1:c.176C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-197791454-C-A
• chr3-197791454-C-T

Variant summary

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

The NM_001365715.1(LRCH3):​c.176C>A​(p.Thr59Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. T59I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRCH3 NM_001365715.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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=0.33614093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRCH3	NM_001365715.1	c.176C>A	p.Thr59Asn	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.176C>A	p.Thr59Asn	missense_variant	Exon 1 of 21	5	NM_001365715.1	ENSP00000393579.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447290 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 718870

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	.;.;.;T;.;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.91	.;D;D;T;D;D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.2	M;M;M;.;M;M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.1	N;.;N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D;.;D;T;D;D
Sift4G	Uncertain	0.016	D;.;D;D;D;D
Polyphen		0.91	P;P;.;D;P;.
Vest4		0.69
MutPred		0.46		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.66
MPC		0.35
ClinPred		0.96	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.49

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: chr3-197518325;