10-48913810-C-T

Variant names:

• chr10-48913810-C-T
• rs1388259938
• NM_001378102.1:c.346G>A

Variant summary

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

The NM_001378102.1(LRRC18):​c.346G>A​(p.Glu116Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. E116Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC18 NM_001378102.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75

Genes affected

LRRC18 (HGNC:23199): (leucine rich repeat containing 18) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

WDFY4 (HGNC:29323): (WDFY family member 4) Predicted to be involved in autophagy. Predicted to act upstream of or within with a positive effect on CD8-positive, alpha-beta T cell activation. Predicted to act upstream of or within antigen processing and presentation and cellular response to virus. Predicted to be located in early endosome and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000241577 (HGNC:):

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 rank	MANE	Protein	UniProt
LRRC18	NM_001378102.1	c.346G>A	p.Glu116Lys	missense_variant	Exon 3 of 4	ENST00000374160.8	NP_001365031.1
WDFY4	NM_001394531.1	c.7586+11947C>T		intron_variant	Intron 47 of 61	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC18	ENST00000374160.8	c.346G>A	p.Glu116Lys	missense_variant	Exon 3 of 4	1	NM_001378102.1	ENSP00000363275.3
WDFY4	ENST00000325239.12	c.7586+11947C>T		intron_variant	Intron 47 of 61	5	NM_001394531.1	ENSP00000320563.5
ENSG00000241577	ENST00000430438.1	n.173+18676G>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	4.0	H
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.27
Sift	Benign	0.28	T
Sift4G	Benign	0.096	T
Polyphen		0.98	D
Vest4		0.65
MutPred		0.55		Gain of MoRF binding (P = 0.0044);
MVP		0.74
MPC		0.042
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.26
gMVP		0.68

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

LitVar

Other links and lift over

dbSNP: rs1388259938; hg19: chr10-50121855;