rs12692566

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002349.4(LY75):​c.3963G>T​(p.Lys1321Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,594,716 control chromosomes in the GnomAD database, including 548,338 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.84 ( 54310 hom., cov: 32)
Exomes 𝑓: 0.83 ( 494028 hom. )

Consequence

LY75
NM_002349.4 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.517
Variant links:
Genes affected
LY75 (HGNC:6729): (lymphocyte antigen 75) Predicted to enable signaling receptor activity. Predicted to be involved in immune response and inflammatory response. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=8.3575503E-7).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LY75NM_002349.4 linkuse as main transcriptc.3963G>T p.Lys1321Asn missense_variant 29/35 ENST00000263636.5
LY75-CD302NM_001198760.1 linkuse as main transcriptc.3963G>T p.Lys1321Asn missense_variant 29/38
LY75-CD302NM_001198759.1 linkuse as main transcriptc.3963G>T p.Lys1321Asn missense_variant 29/39

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LY75ENST00000263636.5 linkuse as main transcriptc.3963G>T p.Lys1321Asn missense_variant 29/351 NM_002349.4 P1O60449-1

Frequencies

GnomAD3 genomes
AF:
0.844
AC:
128269
AN:
152050
Hom.:
54252
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.887
Gnomad AMI
AF:
0.772
Gnomad AMR
AF:
0.880
Gnomad ASJ
AF:
0.828
Gnomad EAS
AF:
0.897
Gnomad SAS
AF:
0.722
Gnomad FIN
AF:
0.796
Gnomad MID
AF:
0.747
Gnomad NFE
AF:
0.823
Gnomad OTH
AF:
0.845
GnomAD3 exomes
AF:
0.826
AC:
193416
AN:
234094
Hom.:
80185
AF XY:
0.819
AC XY:
103768
AN XY:
126704
show subpopulations
Gnomad AFR exome
AF:
0.885
Gnomad AMR exome
AF:
0.878
Gnomad ASJ exome
AF:
0.830
Gnomad EAS exome
AF:
0.898
Gnomad SAS exome
AF:
0.731
Gnomad FIN exome
AF:
0.793
Gnomad NFE exome
AF:
0.821
Gnomad OTH exome
AF:
0.827
GnomAD4 exome
AF:
0.827
AC:
1192413
AN:
1442550
Hom.:
494028
Cov.:
44
AF XY:
0.823
AC XY:
590132
AN XY:
717100
show subpopulations
Gnomad4 AFR exome
AF:
0.893
Gnomad4 AMR exome
AF:
0.879
Gnomad4 ASJ exome
AF:
0.826
Gnomad4 EAS exome
AF:
0.911
Gnomad4 SAS exome
AF:
0.726
Gnomad4 FIN exome
AF:
0.795
Gnomad4 NFE exome
AF:
0.829
Gnomad4 OTH exome
AF:
0.826
GnomAD4 genome
AF:
0.844
AC:
128392
AN:
152166
Hom.:
54310
Cov.:
32
AF XY:
0.840
AC XY:
62503
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.887
Gnomad4 AMR
AF:
0.881
Gnomad4 ASJ
AF:
0.828
Gnomad4 EAS
AF:
0.897
Gnomad4 SAS
AF:
0.723
Gnomad4 FIN
AF:
0.796
Gnomad4 NFE
AF:
0.823
Gnomad4 OTH
AF:
0.847
Alfa
AF:
0.829
Hom.:
122364
Bravo
AF:
0.857
TwinsUK
AF:
0.843
AC:
3125
ALSPAC
AF:
0.823
AC:
3172
ESP6500AA
AF:
0.890
AC:
3915
ESP6500EA
AF:
0.828
AC:
7118
ExAC
AF:
0.824
AC:
99962
Asia WGS
AF:
0.842
AC:
2926
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.051
BayesDel_addAF
Benign
-0.74
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
11
DANN
Benign
0.40
DEOGEN2
Benign
0.021
.;.;T
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.17
T;T;T
MetaRNN
Benign
8.4e-7
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.6
.;.;N
MutationTaster
Benign
1.0
P;P;P;P;P
PROVEAN
Benign
1.9
N;N;N
REVEL
Benign
0.071
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
.;.;B
Vest4
0.053
MutPred
0.56
Loss of ubiquitination at K1321 (P = 0.0155);Loss of ubiquitination at K1321 (P = 0.0155);Loss of ubiquitination at K1321 (P = 0.0155);
MPC
0.055
ClinPred
0.0061
T
GERP RS
4.5
Varity_R
0.18
gMVP
0.33

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: rs12692566; hg19: chr2-160676427; COSMIC: COSV55102106; API