chr5-150412724-C-G

Position:

• chr5-150412724-C-G

Variant summary

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

The NM_001025159.3(CD74):​c.26G>C​(p.Cys9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CD74 NM_001025159.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.204

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]

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=0.075211465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD74	NM_001025159.3	c.26G>C	p.Cys9Ser	missense_variant	1/9	ENST00000009530.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD74	ENST00000009530.13	c.26G>C	p.Cys9Ser	missense_variant	1/9	2	NM_001025159.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.26G>C (p.C9S) alteration is located in exon 1 (coding exon 1) of the CD74 gene. This alteration results from a G to C substitution at nucleotide position 26, causing the cysteine (C) at amino acid position 9 to be replaced by a serine (S). 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	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.59
DEOGEN2	Benign	0.021	.;.;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.71	T;T;T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.075	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L;L;.;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.69	N;N;N;N
REVEL	Benign	0.069
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.0010	B;B;.;B
Vest4		0.20
MutPred		0.25		Gain of phosphorylation at C9 (P = 3e-04);Gain of phosphorylation at C9 (P = 3e-04);Gain of phosphorylation at C9 (P = 3e-04);Gain of phosphorylation at C9 (P = 3e-04);
MVP		0.22
MPC		0.62
ClinPred		0.51	D
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.35
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-149792287;