3-169848231-A-C

Variant names:

• chr3-169848231-A-C
• NM_024727.4:c.1216T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024727.4(LRRC31):​c.1216T>G​(p.Cys406Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC31 NM_024727.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.22

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC31	NM_024727.4	c.1216T>G	p.Cys406Gly	missense_variant	Exon 8 of 9	ENST00000316428.10	NP_079003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC31	ENST00000316428.10	c.1216T>G	p.Cys406Gly	missense_variant	Exon 8 of 9	1	NM_024727.4	ENSP00000325978.5
LRRC31	ENST00000523069.1	c.1216T>G	p.Cys406Gly	missense_variant	Exon 8 of 9	1		ENSP00000429145.1
LRRC31	ENST00000264676.9	c.1048T>G	p.Cys350Gly	missense_variant	Exon 7 of 8	2		ENSP00000264676.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1216T>G (p.C406G) alteration is located in exon 9 (coding exon 8) of the LRRC31 gene. This alteration results from a T to G substitution at nucleotide position 1216, causing the cysteine (C) at amino acid position 406 to be replaced by a glycine (G). 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	0.16
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.054	T;.;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.0	M;.;M
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.5	D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.012	D;T;D
Polyphen		0.99	D;D;.
Vest4		0.70
MutPred		0.70		Loss of methylation at K405 (P = 0.0192);.;Loss of methylation at K405 (P = 0.0192);
MVP		0.69
MPC		0.23
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.69
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-169566019;