7-16566397-G-C

Variant names:

• chr7-16566397-G-C
• rs535134984
• NM_001195280.2:c.512G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001195280.2(LRRC72):​c.512G>C​(p.Arg171Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R171Q) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: LRRC72 NM_001195280.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3220061).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC72	NM_001195280.2	c.512G>C	p.Arg171Pro	missense_variant	Exon 6 of 9	ENST00000401542.3	NP_001182209.1
LRRC72	XM_011515057.2	c.512G>C	p.Arg171Pro	missense_variant	Exon 6 of 10		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC72	ENST00000401542.3	c.512G>C	p.Arg171Pro	missense_variant	Exon 6 of 9	5	NM_001195280.2	ENSP00000384971.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74294

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.3
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.25
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.011	D
Vest4		0.42
MutPred		0.57		Loss of sheet (P = 0.0457);
MVP		0.32
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.53
gMVP		0.63
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs535134984; hg19: chr7-16606022;