21-44456688-C-G

Variant names:

• chr21-44456688-C-G
• NM_030891.6:c.44C>G

Variant summary

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

The NM_030891.6(LRRC3):​c.44C>G​(p.Ser15Cys) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC3 NM_030891.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.770

Genes affected

LRRC3 (HGNC:14965): (leucine rich repeat containing 3) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09379551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC3	NM_030891.6	c.44C>G	p.Ser15Cys	missense_variant	Exon 2 of 2	ENST00000291592.6	NP_112153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC3	ENST00000291592.6	c.44C>G	p.Ser15Cys	missense_variant	Exon 2 of 2	1	NM_030891.6	ENSP00000291592.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.44C>G (p.S15C) alteration is located in exon 2 (coding exon 1) of the LRRC3 gene. This alteration results from a C to G substitution at nucleotide position 44, causing the serine (S) at amino acid position 15 to be replaced by a cysteine (C). 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	0.085
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.73
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.10
Sift	Benign	0.14	T
Sift4G	Benign	0.13	T
Polyphen		0.14	B
Vest4		0.11
MutPred		0.33		Loss of disorder (P = 0.0495);
MVP		0.60
MPC		0.37
ClinPred		0.066	T
GERP RS		3.5
Varity_R		0.063
gMVP		0.65

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: chr21-45876571;