20-23084584-G-T

Variant names:

• chr20-23084584-G-T
• rs767867854
• NM_012072.4:c.1609C>A

Variant summary

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

The NM_012072.4(CD93):​c.1609C>A​(p.Pro537Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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: 34)
• Consequence: CD93 NM_012072.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

Genes affected

CD93 (HGNC:15855): (CD93 molecule) The protein encoded by this gene is a cell-surface glycoprotein and type I membrane protein that was originally identified as a myeloid cell-specific marker. The encoded protein was once thought to be a receptor for C1q, but now is thought to instead be involved in intercellular adhesion and in the clearance of apoptotic cells. The intracellular cytoplasmic tail of this protein has been found to interact with moesin, a protein known to play a role in linking transmembrane proteins to the cytoskeleton and in the remodelling of the cytoskeleton. [provided by RefSeq, Jul 2008]

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=0.084404975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD93	NM_012072.4	c.1609C>A	p.Pro537Thr	missense_variant	Exon 1 of 2	ENST00000246006.5	NP_036204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD93	ENST00000246006.5	c.1609C>A	p.Pro537Thr	missense_variant	Exon 1 of 2	1	NM_012072.4	ENSP00000246006.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 34

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: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 58

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.7
DANN	Benign	0.74
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Benign	0.086	T
Sift4G	Uncertain	0.011	D
Polyphen		0.14	B
Vest4		0.069
MutPred		0.23		Gain of glycosylation at P537 (P = 0.0429);
MVP		0.89
MPC		0.085
ClinPred		0.063	T
GERP RS		-3.8
Varity_R		0.048
gMVP		0.40

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

Other links and lift over

dbSNP: rs767867854; hg19: chr20-23065221;