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GeneBe

6-31717799-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021246.4(LY6G6D):c.397G>A(p.Gly133Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000683 in 1,609,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

LY6G6D
NM_021246.4 missense

Scores

2
3
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.567
Variant links:
Genes affected
LY6G6D (HGNC:13935): (lymphocyte antigen 6 family member G6D) LY6G6D 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, Apr 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.086159706).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LY6G6DNM_021246.4 linkuse as main transcriptc.397G>A p.Gly133Arg missense_variant 3/3 ENST00000375825.8
LY6G6F-LY6G6DNM_001353334.2 linkuse as main transcriptc.1144G>A p.Gly382Arg missense_variant 6/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LY6G6DENST00000375825.8 linkuse as main transcriptc.397G>A p.Gly133Arg missense_variant 3/31 NM_021246.4 P1
LY6G6DENST00000375824.1 linkuse as main transcriptc.518G>A p.Arg173Gln missense_variant 3/31
LY6G6DENST00000479334.1 linkuse as main transcriptn.488G>A non_coding_transcript_exon_variant 2/21

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152220
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000604
AC:
15
AN:
248234
Hom.:
0
AF XY:
0.0000744
AC XY:
10
AN XY:
134388
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000100
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000974
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000638
AC:
93
AN:
1457424
Hom.:
0
Cov.:
29
AF XY:
0.0000538
AC XY:
39
AN XY:
724798
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.0000505
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000196
Gnomad4 NFE exome
AF:
0.0000657
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152338
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.000192
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000708
Hom.:
0
Bravo
AF:
0.000110
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 28, 2023The c.397G>A (p.G133R) alteration is located in exon 3 (coding exon 3) of the LY6G6D gene. This alteration results from a G to A substitution at nucleotide position 397, causing the glycine (G) at amino acid position 133 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.45
Cadd
Benign
19
Dann
Uncertain
0.99
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.12
N
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.086
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N
PROVEAN
Uncertain
-2.9
D;D
REVEL
Benign
0.033
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.75
.;P
Vest4
0.20
MutPred
0.29
.;Gain of solvent accessibility (P = 0.0037);
MVP
0.45
MPC
0.17
ClinPred
0.23
T
GERP RS
1.3
Varity_R
0.041
gMVP
0.31

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs368565028; hg19: chr6-31685576; API