Genetic Variant LRRC72:p.Leu17Pro (chr7-16527002-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.50T>C(p.Leu17Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,387,568 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L17R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LRRC72
NM_001195280.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.99

Publications

0 publications found

Variant links:

Genes affected

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

LRRC72 links:

SOSTDC1 (HGNC:21748): (sclerostin domain containing 1) This gene is a member of the sclerostin family and encodes an N-glycosylated, secreted protein with a C-terminal cystine knot-like domain. This protein functions as a bone morphogenetic protein (BMP) antagonist. Specifically, it directly associates with BMPs, prohibiting them from binding their receptors, thereby regulating BMP signaling during cellular proliferation, differentiation, and programmed cell death. [provided by RefSeq, Jul 2008]

SOSTDC1 links:

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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=0.13188148).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC72	NM_001195280.2 link	c.50T>C	p.Leu17Pro	missense_variant	Exon 1 of 9	ENST00000401542.3	NP_001182209.1	A6NJI9
LRRC72	XM_011515057.2 link	c.50T>C	p.Leu17Pro	missense_variant	Exon 1 of 10		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRRC72	ENST00000401542.3 link	c.50T>C	p.Leu17Pro	missense_variant	Exon 1 of 9	5	NM_001195280.2	ENSP00000384971.2	A6NJI9
LRRC72	ENST00000382124.7 link	n.50T>C		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000371558.3	F8VSY1
LRRC72	ENST00000482711.1 link	n.113T>C		non_coding_transcript_exon_variant	Exon 1 of 3	2
SOSTDC1	ENST00000396652.1 link	c.-320+3185A>G		intron_variant	Intron 1 of 4	2		ENSP00000379889.1	Q6X4U4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1387568

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684792

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35736

South Asian (SAS)

AF:

0.00

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078902

Other (OTH)

AF:

0.00

AC:

AN:

57928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.12

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.014

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.36

M_CAP

Benign

0.0024

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.20

PhyloP100

-2.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.89

REVEL

Benign

0.061

Sift

Benign

0.089

Sift4G

Benign

0.094

Vest4

0.076

MutPred

0.52

Gain of glycosylation at L17 (P = 0.0154);

MVP

0.35

ClinPred

0.062

GERP RS

-6.4

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.11

gMVP

0.39

Mutation Taster

=98/2

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

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7-16527002-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over