chr21-44456982-G-C

Variant names:

• chr21-44456982-G-C
• rs749731059
• NM_030891.6:c.338G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030891.6(LRRC3):​c.338G>C​(p.Gly113Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G113E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRRC3 NM_030891.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.72
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.120819).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030891.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC3	NM_030891.6	MANE Select	c.338G>C	p.Gly113Ala	missense	Exon 2 of 2	NP_112153.1	Q9BY71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC3	ENST00000291592.6	TSL:1 MANE Select	c.338G>C	p.Gly113Ala	missense	Exon 2 of 2	ENSP00000291592.4	Q9BY71
	LRRC3	ENST00000885220.1		c.338G>C	p.Gly113Ala	missense	Exon 2 of 2	ENSP00000555279.1
	LRRC3	ENST00000885221.1		c.338G>C	p.Gly113Ala	missense	Exon 2 of 2	ENSP00000555280.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454702 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724018

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111844

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.87
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	-0.015	N
PhyloP100		4.7
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.24
Sift	Benign	0.27	T
Sift4G	Benign	0.50	T
Polyphen		0.013	B
Vest4		0.11
MutPred		0.36		Gain of helix (P = 0.132)
MVP		0.90
MPC		0.32
ClinPred		0.81	D
GERP RS		4.8
Varity_R		0.077
gMVP		0.37
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs749731059; hg19: chr21-45876865;