6-14135126-A-G

Position:

• chr6-14135126-A-G

Variant summary

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

The ENST00000379153.4(CD83):​c.508A>G​(p.Ser170Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: CD83 ENST00000379153.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

Genes affected

CD83 (HGNC:1703): (CD83 molecule) The protein encoded by this gene is a single-pass type I membrane protein and member of the immunoglobulin superfamily of receptors. The encoded protein may be involved in the regulation of antigen presentation. A soluble form of this protein can bind to dendritic cells and inhibit their maturation. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 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=0.2346963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD83	NM_004233.4	c.508A>G	p.Ser170Gly	missense_variant	5/5	ENST00000379153.4	NP_004224.1
CD83	NM_001040280.3	c.505A>G	p.Ser169Gly	missense_variant	5/5		NP_001035370.1
CD83	NM_001251901.1	c.331A>G	p.Ser111Gly	missense_variant	5/5		NP_001238830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD83	ENST00000379153.4	c.508A>G	p.Ser170Gly	missense_variant	5/5	1	NM_004233.4	ENSP00000368450	P1
CD83	ENST00000612003.4	c.331A>G	p.Ser111Gly	missense_variant	5/5	4		ENSP00000480760

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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 29, 2024

The c.508A>G (p.S170G) alteration is located in exon 5 (coding exon 5) of the CD83 gene. This alteration results from a A to G substitution at nucleotide position 508, causing the serine (S) at amino acid position 170 to be replaced by a glycine (G). 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	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	.;M
MutationTaster	Benign	0.63	D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.2	.;N
REVEL	Benign	0.25
Sift	Uncertain	0.027	.;D
Sift4G	Uncertain	0.031	D;D
Polyphen		0.98	.;D
Vest4		0.23
MutPred		0.62		.;Gain of loop (P = 0.0166);
MVP		0.44
MPC		0.81
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.16
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-14135357; COSMIC: COSV64788338;