GeneBe

6-43507605-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001012974.4(LRRC73):​c.731C>T​(p.Pro244Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000812 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

LRRC73
NM_001012974.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.58

Publications

0 publications found
Variant links:
Genes affected
LRRC73 (HGNC:21375): (leucine rich repeat containing 73)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.15023947).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC73NM_001012974.4 linkc.731C>T p.Pro244Leu missense_variant Exon 5 of 6 ENST00000372441.2 NP_001012992.1 Q5JTD7
LRRC73NM_001271882.2 linkc.362C>T p.Pro121Leu missense_variant Exon 5 of 6 NP_001258811.1 Q5JTD7Q3B825

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC73ENST00000372441.2 linkc.731C>T p.Pro244Leu missense_variant Exon 5 of 6 1 NM_001012974.4 ENSP00000361518.1 Q5JTD7

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152142
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000718
AC:
18
AN:
250864
AF XY:
0.0000810
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000828
AC:
121
AN:
1461804
Hom.:
0
Cov.:
32
AF XY:
0.0000811
AC XY:
59
AN XY:
727200
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.0000894
AC:
4
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86258
European-Finnish (FIN)
AF:
0.0000187
AC:
1
AN:
53344
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000998
AC:
111
AN:
1112008
Other (OTH)
AF:
0.0000662
AC:
4
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.482
Heterozygous variant carriers
0
9
18
26
35
44
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<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:
0.0000657
AC:
10
AN:
152142
Hom.:
0
Cov.:
33
AF XY:
0.0000673
AC XY:
5
AN XY:
74314
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41426
American (AMR)
AF:
0.00
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000147
AC:
10
AN:
68030
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000132
Hom.:
0
Bravo
AF:
0.000117
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 28, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.731C>T (p.P244L) alteration is located in exon 5 (coding exon 5) of the LRRC73 gene. This alteration results from a C to T substitution at nucleotide position 731, causing the proline (P) at amino acid position 244 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Benign
0.96
DEOGEN2
Benign
0.077
T
Eigen
Benign
0.054
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
PhyloP100
6.6
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.055
Sift
Benign
0.17
T
Sift4G
Benign
0.25
T
Polyphen
0.0030
B
Vest4
0.44
MVP
0.043
MPC
0.76
ClinPred
0.11
T
GERP RS
5.9
Varity_R
0.19
gMVP
0.55
Mutation Taster
=84/16
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

Publications

Other links and lift over

dbSNP: rs762857727; hg19: chr6-43475343; API