7-16581383-T-C

Position:

• chr7-16581383-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195280.2(LRRC72):​c.758T>C​(p.Met253Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0000021 (0 hom.)
• Consequence: LRRC72 NM_001195280.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66

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=0.22269806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC72	NM_001195280.2	c.758T>C	p.Met253Thr	missense_variant	9/9	ENST00000401542.3	NP_001182209.1
LRRC72	XM_011515057.2	c.851T>C	p.Met284Thr	missense_variant	10/10		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC72	ENST00000401542.3	c.758T>C	p.Met253Thr	missense_variant	9/9	5	NM_001195280.2	ENSP00000384971.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000666 AC: 1 AN: 150208 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 80438

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: 0.0000449

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1397414 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 689200

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: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

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

Mar 30, 2024

The c.758T>C (p.M253T) alteration is located in exon 9 (coding exon 9) of the LRRC72 gene. This alteration results from a T to C substitution at nucleotide position 758, causing the methionine (M) at amino acid position 253 to be replaced by a threonine (T). 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	0.30
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.81
DEOGEN2	Benign	0.030	T
Eigen	Benign	0.012
Eigen_PC	Benign	0.057
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.087
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Vest4		0.39
MutPred		0.35		Gain of sheet (P = 0.039);
MVP		0.24
ClinPred		0.25	T
GERP RS		3.5
Varity_R		0.39
gMVP		0.34

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

LitVar

Other links and lift over

dbSNP: rs768488761; hg19: chr7-16621008;