Genetic Variant LRRC72:p.Ala191Val (chr7-16567445-C-T) – 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.572C>T(p.Ala191Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000728 in 1,373,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0000073 ( 0 hom. )

Consequence

LRRC72
NM_001195280.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

Publications

1 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=0.1359447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC72	NM_001195280.2 link	c.572C>T	p.Ala191Val	missense_variant	Exon 7 of 9	ENST00000401542.3	NP_001182209.1	A6NJI9
LRRC72	XM_011515057.2 link	c.572C>T	p.Ala191Val	missense_variant	Exon 7 of 10		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC72	ENST00000401542.3 link	c.572C>T	p.Ala191Val	missense_variant	Exon 7 of 9	5	NM_001195280.2	ENSP00000384971.2		A6NJI9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000732

AC:

AN:

136674

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:

0.0000196

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000728

AC:

AN:

1373828

Hom.:

Cov.:

AF XY:

0.00000443

AC XY:

AN XY:

677476

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30494

American (AMR)

AF:

0.0000316

AC:

AN:

31692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24302

East Asian (EAS)

AF:

0.00

AC:

AN:

35250

South Asian (SAS)

AF:

0.00

AC:

AN:

74512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5566

European-Non Finnish (NFE)

AF:

0.00000843

AC:

AN:

1067742

Other (OTH)

AF:

0.00

AC:

AN:

56844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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

Dec 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.572C>T (p.A191V) alteration is located in exon 7 (coding exon 7) of the LRRC72 gene. This alteration results from a C to T substitution at nucleotide position 572, causing the alanine (A) at amino acid position 191 to be replaced by a valine (V). 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

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Benign

-0.015

Eigen_PC

Benign

-0.037

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.71

M_CAP

Benign

0.017

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.8

PhyloP100

3.1

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.0

REVEL

Benign

0.13

Sift

Benign

0.30

Sift4G

Benign

0.13

Vest4

0.14

MutPred

0.59

Gain of methylation at K190 (P = 0.0354);

MVP

0.19

ClinPred

0.21

GERP RS

4.9

Varity_R

0.061

gMVP

0.10

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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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7-16567445-C-T

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