rs776174712

Variant names:

• chr10-48913783-C-A
• NM_001378102.1:c.373G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-48913783-C-A
• chr10-48913783-C-G
• chr10-48913783-C-T

Variant summary

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

The NM_001378102.1(LRRC18):​c.373G>T​(p.Ala125Ser) 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. 15/21 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. A125T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC18 NM_001378102.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072551966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC18	NM_001378102.1	c.373G>T	p.Ala125Ser	missense_variant	Exon 3 of 4	ENST00000374160.8	NP_001365031.1
WDFY4	NM_001394531.1	c.7586+11920C>A		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.373G>T	p.Ala125Ser	missense_variant	Exon 3 of 4	1	NM_001378102.1	ENSP00000363275.3
WDFY4	ENST00000325239.12	c.7586+11920C>A		intron_variant	Intron 47 of 61	5	NM_001394531.1	ENSP00000320563.5
ENSG00000241577	ENST00000430438.1	n.173+18703G>T		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.91
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.073	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.29	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.034
Sift	Benign	0.46	T
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.034
MutPred		0.31		Gain of disorder (P = 0.0913);
MVP		0.088
MPC		0.014
ClinPred		0.14	T
GERP RS		3.6
Varity_R		0.039
gMVP		0.28

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: chr10-50121828;