dbSNP rs201645357: LRCH3:p.Leu94Phe (chr3-197814925-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001365715.1(LRCH3):c.280C>T(p.Leu94Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000291 in 1,594,220 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

LRCH3
NM_001365715.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61

Publications

2 publications found

Variant links:

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]

LRCH3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010888964).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRCH3	NM_001365715.1	MANE Select	c.280C>T	p.Leu94Phe	missense	Exon 2 of 21	NP_001352644.1	Q96II8-1
LRCH3	NM_001363887.1		c.280C>T	p.Leu94Phe	missense	Exon 2 of 21	NP_001350816.1	Q96II8-2
LRCH3	NM_001365716.1		c.280C>T	p.Leu94Phe	missense	Exon 2 of 20	NP_001352645.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRCH3	ENST00000425562.7	TSL:5 MANE Select	c.280C>T	p.Leu94Phe	missense	Exon 2 of 21	ENSP00000393579.2	Q96II8-1
LRCH3	ENST00000334859.8	TSL:1	c.280C>T	p.Leu94Phe	missense	Exon 2 of 19	ENSP00000334375.4	Q96II8-3
LRCH3	ENST00000428136.2	TSL:5	c.280C>T	p.Leu94Phe	missense	Exon 2 of 21	ENSP00000394763.2	Q96II8-2

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000217

AC:

AN:

234732

AF XY:

0.000252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000338

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000392

Gnomad OTH exome

AF:

0.000529

GnomAD4 exome

AF:

0.000275

AC:

396

AN:

1441980

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

200

AN XY:

716194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32592

American (AMR)

AF:

0.0000246

AC:

AN:

40676

Ashkenazi Jewish (ASJ)

AF:

0.0000388

AC:

AN:

25776

East Asian (EAS)

AF:

0.00

AC:

AN:

38992

South Asian (SAS)

AF:

0.0000753

AC:

AN:

79676

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53170

Middle Eastern (MID)

AF:

0.000350

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.000334

AC:

369

AN:

1105726

Other (OTH)

AF:

0.000268

AC:

AN:

59654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000447

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41548

American (AMR)

AF:

0.000196

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000425

Hom.:

Bravo

AF:

0.000461

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000198

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

M_CAP

Benign

0.012

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

3.6

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.7

REVEL

Benign

0.22

Sift

Benign

0.55

Sift4G

Benign

0.43

Polyphen

1.0

Vest4

0.83

MVP

0.44

MPC

0.41

ClinPred

0.36

GERP RS

4.7

Varity_R

0.12

gMVP

0.59

Mutation Taster

=67/33

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over