3-197791302-T-C

Variant names:

• chr3-197791302-T-C
• rs143455842
• NM_001365715.1:c.24T>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001365715.1(LRCH3):​c.24T>C​(p.Ala8Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,608,846 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (2 hom.)
• Consequence: LRCH3 NM_001365715.1 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.491

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-197791302-T-C is Benign according to our data. Variant chr3-197791302-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3035137.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.491 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRCH3	NM_001365715.1	c.24T>C	p.Ala8Ala	synonymous_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.24T>C	p.Ala8Ala	synonymous_variant	Exon 1 of 21	5	NM_001365715.1	ENSP00000393579.2

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 155 AN: 152184 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000968 AC: 226 AN: 233446 Hom.: 0 AF XY: 0.00103 AC XY: 132 AN XY: 127994

Gnomad AFR exome AF: 0.000216

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000668

Gnomad FIN exome AF: 0.000542

Gnomad NFE exome AF: 0.00139

Gnomad OTH exome AF: 0.00142

GnomAD4 exome AF: 0.00143 AC: 2084 AN: 1456544 Hom.: 2 Cov.: 32 AF XY: 0.00142 AC XY: 1028 AN XY: 724482

Gnomad4 AFR exome AF: 0.000302

Gnomad4 AMR exome AF: 0.00133

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000665

Gnomad4 FIN exome AF: 0.000409

Gnomad4 NFE exome AF: 0.00168

Gnomad4 OTH exome AF: 0.00110

GnomAD4 genome AF: 0.00102 AC: 155 AN: 152302 Hom.: 0 Cov.: 31 AF XY: 0.000859 AC XY: 64 AN XY: 74468

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.00118

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

LRCH3-related disorder Benign:1

Sep 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.2
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143455842; hg19: chr3-197518173;