3-169861700-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_024727.4(LRRC31):c.289G>C(p.Gly97Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LRRC31 NM_024727.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.433

Genes affected

LRRC31 (HGNC:26261): (leucine rich repeat containing 31)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07271603).
• BP6: Variant 3-169861700-C-G is Benign according to our data. Variant chr3-169861700-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3120537.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC31	NM_024727.4	c.289G>C	p.Gly97Arg	missense_variant	2/9	ENST00000316428.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC31	ENST00000316428.10	c.289G>C	p.Gly97Arg	missense_variant	2/9	1	NM_024727.4	P1
LRRC31	ENST00000523069.1	c.289G>C	p.Gly97Arg	missense_variant	2/9	1
LRRC31	ENST00000264676.9	c.289G>C	p.Gly97Arg	missense_variant	2/8	2
LRRC31	ENST00000397805.2	n.356G>C		non_coding_transcript_exon_variant	2/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461746 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	0.15
Dann	Benign	0.55
DEOGEN2	Benign	0.0066	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.31	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.041
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.18
MutPred		0.45		Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);
MVP		0.25
MPC		0.033
ClinPred		0.067	T
GERP RS		-0.13
Varity_R		0.038
gMVP		0.29

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

Other links and lift over

dbSNP: rs1781165868; hg19: chr3-169579488;