dbSNP rs750518494: LRCH3:p.Pro73Ser (chr3-197791495-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001365715.1(LRCH3):c.217C>T(p.Pro73Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,447,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

LRCH3
NM_001365715.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.91

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.217C>T	p.Pro73Ser	missense	Exon 1 of 21	NP_001352644.1	Q96II8-1
LRCH3	NM_001363887.1		c.217C>T	p.Pro73Ser	missense	Exon 1 of 21	NP_001350816.1	Q96II8-2
LRCH3	NM_001365716.1		c.217C>T	p.Pro73Ser	missense	Exon 1 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.217C>T	p.Pro73Ser	missense	Exon 1 of 21	ENSP00000393579.2	Q96II8-1
LRCH3	ENST00000334859.8	TSL:1	c.217C>T	p.Pro73Ser	missense	Exon 1 of 19	ENSP00000334375.4	Q96II8-3
LRCH3	ENST00000428136.2	TSL:5	c.217C>T	p.Pro73Ser	missense	Exon 1 of 21	ENSP00000394763.2	Q96II8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000453

AC:

AN:

220772

AF XY:

0.0000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000408

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1447900

Hom.:

Cov.:

AF XY:

0.0000236

AC XY:

AN XY:

719768

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32042

American (AMR)

AF:

0.00

AC:

AN:

43572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25622

East Asian (EAS)

AF:

0.00

AC:

AN:

38508

South Asian (SAS)

AF:

0.000154

AC:

AN:

84500

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1107064

Other (OTH)

AF:

0.00

AC:

AN:

59734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000665

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

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.74

MetaSVM

Uncertain

-0.076

MutationAssessor

Uncertain

2.6

PhyloP100

6.9

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-6.7

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.80

MutPred

0.42

Gain of phosphorylation at P73 (P = 0.0261)

MVP

0.82

MPC

0.47

ClinPred

0.91

GERP RS

4.7

PromoterAI

-0.092

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.60

Mutation Taster

=26/74

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over