7-16567445-C-T

Position:

• chr7-16567445-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 15/20 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.09

Genes affected

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

ACMG classification

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=0.1359447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC72	NM_001195280.2	c.572C>T	p.Ala191Val	missense_variant	7/9	ENST00000401542.3	NP_001182209.1
LRRC72	XM_011515057.2	c.572C>T	p.Ala191Val	missense_variant	7/10		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC72	ENST00000401542.3	c.572C>T	p.Ala191Val	missense_variant	7/9	5	NM_001195280.2	ENSP00000384971.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000732 AC: 1 AN: 136674 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 74166

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 SAS 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: 10 AN: 1373828 Hom.: 0 Cov.: 30 AF XY: 0.00000443 AC XY: 3 AN XY: 677476

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000316

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000843

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

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	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.015
Eigen_PC	Benign	-0.037
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.13
Sift	Benign	0.30	T
Sift4G	Benign	0.13	T
Vest4		0.14
MutPred		0.59		Gain of methylation at K190 (P = 0.0354);
MVP		0.19
ClinPred		0.21	T
GERP RS		4.9
Varity_R		0.061
gMVP		0.10

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

LitVar

Other links and lift over

dbSNP: rs1247892205; hg19: chr7-16607070;