Variant 7-16537656-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001195280.2(LRRC72):c.194G>A(p.Arg65Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000131 in 1,526,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

LRRC72
NM_001195280.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

Variant links:

Genes affected

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

LRRC72 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11824033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC72	NM_001195280.2 linkuse as main transcript	c.194G>A	p.Arg65Lys	missense_variant	3/9	ENST00000401542.3	NP_001182209.1	A6NJI9
LRRC72	XM_011515057.2 linkuse as main transcript	c.194G>A	p.Arg65Lys	missense_variant	3/10		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC72	ENST00000401542.3 linkuse as main transcript	c.194G>A	p.Arg65Lys	missense_variant	3/9	5	NM_001195280.2	ENSP00000384971.2	A6NJI9
LRRC72	ENST00000382124.7 linkuse as main transcript	n.*171G>A		non_coding_transcript_exon_variant	4/4	3		ENSP00000371558.3	F8VSY1
LRRC72	ENST00000382124.7 linkuse as main transcript	n.*171G>A		3_prime_UTR_variant	4/4	3		ENSP00000371558.3	F8VSY1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151666

Hom.:

Cov.:

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:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.27e-7

AC:

AN:

1374878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

678006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151666

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74030

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 23, 2023

The c.194G>A (p.R65K) alteration is located in exon 3 (coding exon 3) of the LRRC72 gene. This alteration results from a G to A substitution at nucleotide position 194, causing the arginine (R) at amino acid position 65 to be replaced by a lysine (K). 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

0.20

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.019

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.50

M_CAP

Benign

0.0095

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.095

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

REVEL

Benign

0.070

Sift

Benign

0.25

Sift4G

Benign

0.84

Vest4

0.16

MutPred

0.46

Gain of methylation at R65 (P = 0.0063);

MVP

0.14

ClinPred

0.44

GERP RS

4.5

Varity_R

0.13

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over