16-67378673-G-C

Variant summary

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

The NM_018296.6(LRRC36):c.1891G>C(p.Ala631Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LRRC36 NM_018296.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.154

Genes affected

LRRC36 (HGNC:25615): (leucine rich repeat containing 36)

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=0.072451204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC36	NM_018296.6	c.1891G>C	p.Ala631Pro	missense_variant	12/14	ENST00000329956.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC36	ENST00000329956.11	c.1891G>C	p.Ala631Pro	missense_variant	12/14	1	NM_018296.6	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

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

Jan 23, 2024

The c.1891G>C (p.A631P) alteration is located in exon 12 (coding exon 12) of the LRRC36 gene. This alteration results from a G to C substitution at nucleotide position 1891, causing the alanine (A) at amino acid position 631 to be replaced by a proline (P). 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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	13
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0037	T;.;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.85	N;N;N
REVEL	Benign	0.046
Sift	Uncertain	0.010	D;D;T
Sift4G	Uncertain	0.035	D;D;D
Polyphen		0.0010	B;P;.
Vest4		0.12
MutPred		0.24		Gain of disorder (P = 0.072);.;.;
MVP		0.41
MPC		0.29
ClinPred		0.21	T
GERP RS		0.92
Varity_R		0.17
gMVP		0.14

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: chr16-67412576;