Variant rs12692566 details in Genebe, Genetics Data Aggregator

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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

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

Exomes 𝑓: 0.83 ( 494028 hom. )

Consequence

LY75
NM_002349.4 missense

Scores

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]

LY75 links:

LY75-CD302 (HGNC:38828): (LY75-CD302 readthrough) This locus represents naturally occurring read-through transcription between the neighboring lymphocyte antigen 75 (LY75) and CD302 molecule (CD302) genes. Alternative splicing results in multiple transcript variants encoding fusion products that share sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

LY75-CD302 links:

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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	Protein	UniProt
LY75	NM_002349.4 link	c.3963G>T	p.Lys1321Asn	missense_variant	29/35	ENST00000263636.5	NP_002340.2	O60449-1Q59H44
LY75-CD302	NM_001198759.1 link	c.3963G>T	p.Lys1321Asn	missense_variant	29/39		NP_001185688.1	O60449-2
LY75-CD302	NM_001198760.1 link	c.3963G>T	p.Lys1321Asn	missense_variant	29/38		NP_001185689.1	O60449-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LY75	ENST00000263636.5 link	c.3963G>T	p.Lys1321Asn	missense_variant	29/35	1	NM_002349.4	ENSP00000263636.4	O60449-1
LY75-CD302	ENST00000504764.5 link	c.3963G>T	p.Lys1321Asn	missense_variant	29/39	2		ENSP00000423463.1
LY75-CD302	ENST00000505052.1 link	c.3963G>T	p.Lys1321Asn	missense_variant	29/38	2		ENSP00000421035.1

Frequencies

GnomAD3 genomes

AF:

0.844

AC:

128269

AN:

152050

Hom.:

54252

Cov.:

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.:

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.:

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

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.40

DEOGEN2

Benign

0.021

.;.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.17

T;T;T

MetaRNN

Benign

8.4e-7

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

.;.;N

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over