NM_001025159.3:c.137G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001025159.3(CD74):​c.137G>T​(p.Arg46Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,607,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CD74
NM_001025159.3 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.13
Variant links:
Genes affected
CD74 (HGNC:1697): (CD74 molecule) The protein encoded by this gene associates with class II major histocompatibility complex (MHC) and is an important chaperone that regulates antigen presentation for immune response. It also serves as cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF) which, when bound to the encoded protein, initiates survival pathways and cell proliferation. This protein also interacts with amyloid precursor protein (APP) and suppresses the production of amyloid beta (Abeta). Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD74NM_001025159.3 linkc.137G>T p.Arg46Leu missense_variant Exon 2 of 9 ENST00000009530.13 NP_001020330.1 P04233-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD74ENST00000009530.13 linkc.137G>T p.Arg46Leu missense_variant Exon 2 of 9 2 NM_001025159.3 ENSP00000009530.7 P04233-1

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151854
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000211
AC:
5
AN:
237298
Hom.:
0
AF XY:
0.0000233
AC XY:
3
AN XY:
128550
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000466
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000549
AC:
8
AN:
1455880
Hom.:
0
Cov.:
31
AF XY:
0.00000691
AC XY:
5
AN XY:
723772
show subpopulations
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:
0.00000721
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151854
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74132
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000412
AC:
5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.084
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
.;.;T;D
Eigen
Benign
0.053
Eigen_PC
Benign
-0.0016
FATHMM_MKL
Benign
0.50
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.94
D;D;D;D
MetaSVM
Uncertain
-0.11
T
MutationAssessor
Uncertain
2.6
M;M;.;M
PrimateAI
Benign
0.35
T
PROVEAN
Pathogenic
-4.4
D;D;D;D
REVEL
Uncertain
0.32
Sift
Uncertain
0.0060
D;D;D;D
Sift4G
Uncertain
0.025
D;D;D;D
Polyphen
0.52
P;P;.;D
Vest4
0.69
MutPred
0.83
Gain of ubiquitination at K43 (P = 0.0528);Gain of ubiquitination at K43 (P = 0.0528);Gain of ubiquitination at K43 (P = 0.0528);Gain of ubiquitination at K43 (P = 0.0528);
MVP
0.70
MPC
1.5
ClinPred
0.92
D
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.19
gMVP
0.72

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

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

Other links and lift over

dbSNP: rs201071483; hg19: chr5-149786876; API