6-31672068-C-T

Position:

• chr6-31672068-C-T

Variant summary

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

The NM_021221.3(LY6G5B):​c.392C>T​(p.Ser131Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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. S131Y) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LY6G5B NM_021221.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116

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]

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=0.075170755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY6G5B	NM_021221.3	c.392C>T	p.Ser131Phe	missense_variant	3/3	ENST00000375864.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LY6G5B	ENST00000375864.5	c.392C>T	p.Ser131Phe	missense_variant	3/3	1	NM_021221.3	P1
LY6G5B	ENST00000409525.1	c.227C>T	p.Ser76Phe	missense_variant	2/2	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460810 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726722

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.8
DANN	Benign	0.64
DEOGEN2	Benign	0.050	.;.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.58	T;T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.075	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	.;.;L;.
PROVEAN	Benign	-1.8	.;.;N;D
REVEL	Benign	0.017
Sift	Uncertain	0.021	.;.;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.0	.;.;B;.
Vest4		0.15
MutPred		0.32		.;.;Loss of disorder (P = 0.013);.;
MVP		0.26
MPC		0.11
ClinPred		0.032	T
GERP RS		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.039
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11758242; hg19: chr6-31639845;