20-23084313-C-A

Variant names:

• chr20-23084313-C-A
• rs138693220
• NM_012072.4:c.1880G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_012072.4(CD93):​c.1880G>T​(p.Ser627Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S627N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD93 NM_012072.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.814
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity C1QR1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41967162).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012072.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD93	NM_012072.4	MANE Select	c.1880G>T	p.Ser627Ile	missense	Exon 1 of 2	NP_036204.2	Q9NPY3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD93	ENST00000246006.5	TSL:1 MANE Select	c.1880G>T	p.Ser627Ile	missense	Exon 1 of 2	ENSP00000246006.4	Q9NPY3
	CD93	ENST00000850633.1		n.1880G>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000520912.1	Q9NPY3
	CD93	ENST00000850634.1		n.1880G>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000520913.1	Q9NPY3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727244

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.81
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.66	P
Vest4		0.38
MutPred		0.27		Gain of catalytic residue at S627 (P = 0.0055)
MVP		0.94
MPC		0.24
ClinPred		0.97	D
GERP RS		3.0
Varity_R		0.17
gMVP		0.27
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs138693220; hg19: chr20-23064950;