Genetic Variant LRRC72:p.Met253Thr (chr7-16581383-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001195280.2(LRRC72):c.758T>C(p.Met253Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LRRC72
NM_001195280.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

Publications

0 publications found

Variant links:

Genes affected

LRRC72 (HGNC:42972): (leucine rich repeat containing 72)

LRRC72 links:

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=0.22269806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC72	NM_001195280.2 link	c.758T>C	p.Met253Thr	missense_variant	Exon 9 of 9	ENST00000401542.3	NP_001182209.1	A6NJI9
LRRC72	XM_011515057.2 link	c.851T>C	p.Met284Thr	missense_variant	Exon 10 of 10		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC72	ENST00000401542.3 link	c.758T>C	p.Met253Thr	missense_variant	Exon 9 of 9	5	NM_001195280.2	ENSP00000384971.2		A6NJI9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000666

AC:

AN:

150208

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1397414

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31572

American (AMR)

AF:

0.00

AC:

AN:

35516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25168

East Asian (EAS)

AF:

0.00

AC:

AN:

35698

South Asian (SAS)

AF:

0.0000127

AC:

AN:

78882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078380

Other (OTH)

AF:

0.00

AC:

AN:

58096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 30, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.758T>C (p.M253T) alteration is located in exon 9 (coding exon 9) of the LRRC72 gene. This alteration results from a T to C substitution at nucleotide position 758, causing the methionine (M) at amino acid position 253 to be replaced by a threonine (T). 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

0.30

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.030

Eigen

Benign

0.012

Eigen_PC

Benign

0.057

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.42

M_CAP

Benign

0.0074

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

2.7

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.087

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0060

Vest4

0.39

MutPred

0.35

Gain of sheet (P = 0.039);

MVP

0.24

ClinPred

0.25

GERP RS

3.5

Varity_R

0.39

gMVP

0.34

Mutation Taster

=99/1

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.

7-16581383-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over