3-169854826-G-T

Variant summary

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

The NM_024727.4(LRRC31):c.978C>A(p.Asp326Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRRC31 NM_024727.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.512

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC31	NM_024727.4	c.978C>A	p.Asp326Glu	missense_variant	6/9	ENST00000316428.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC31	ENST00000316428.10	c.978C>A	p.Asp326Glu	missense_variant	6/9	1	NM_024727.4	P1
LRRC31	ENST00000523069.1	c.978C>A	p.Asp326Glu	missense_variant	6/9	1
LRRC31	ENST00000264676.9	c.810C>A	p.Asp270Glu	missense_variant	5/8	2
LRRC31	ENST00000397805.2	n.1045C>A		non_coding_transcript_exon_variant	6/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459770 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726156

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jun 24, 2022

The c.978C>A (p.D326E) alteration is located in exon 7 (coding exon 6) of the LRRC31 gene. This alteration results from a C to A substitution at nucleotide position 978, causing the aspartic acid (D) at amino acid position 326 to be replaced by a glutamic acid (E). 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	Pathogenic	0.69
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	15
Dann	Uncertain	0.99
DEOGEN2	Benign	0.020	T;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.50	D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.7	M;.;M
MutationTaster	Benign	0.95	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.014	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.58
MutPred		0.35		Loss of helix (P = 0.2662);.;Loss of helix (P = 0.2662);
MVP		0.61
MPC		0.22
ClinPred		0.89	D
GERP RS		1.6
Varity_R		0.16
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr3-169572614;