NM_021221.3:c.238C>A

Variant names:

• chr6-31671914-C-A
• rs139883690
• NM_021221.3:c.238C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021221.3(LY6G5B):​c.238C>A​(p.Arg80Ser) 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. 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. R80H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LY6G5B NM_021221.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 1 publications found

Genes affected

LY6G5B (HGNC:13931): (lymphocyte antigen 6 family member G5B) LY6G5B belongs to a cluster of leukocyte antigen-6 (LY6) genes located in the major histocompatibility complex (MHC) class III region on chromosome 6. Members of the LY6 superfamily typically contain 70 to 80 amino acids, including 8 to 10 cysteines. Most LY6 proteins are attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor that is directly involved in signal transduction (Mallya et al., 2002 [PubMed 12079290]).[supplied by OMIM, Mar 2008]

ENSG00000263020 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32177955).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021221.3. 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
	LY6G5B	NM_021221.3	MANE Select	c.238C>A	p.Arg80Ser	missense	Exon 3 of 3	NP_067044.2	A0A1U9X7Y3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY6G5B	ENST00000375864.5	TSL:1 MANE Select	c.238C>A	p.Arg80Ser	missense	Exon 3 of 3	ENSP00000365024.4	Q8NDX9-1
	ENSG00000263020	ENST00000617558.2	TSL:1	c.547C>A	p.Arg183Ser	missense	Exon 6 of 6	ENSP00000483989.2	N0E472
	LY6G5B	ENST00000409525.1	TSL:1	c.73C>A	p.Arg25Ser	missense	Exon 2 of 2	ENSP00000386365.1	Q8NDX9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.9
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.12
Sift	Benign	0.068	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.83	P
Vest4		0.40
MutPred		0.70		Loss of sheet (P = 0.0181)
MVP		0.35
MPC		0.46
ClinPred		0.79	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.23
Mutation Taster		=87/13	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: rs139883690; hg19: chr6-31639691;