NM_012072.4:c.1621C>A

Variant names:

• chr20-23084572-G-T
• rs3746731
• NM_012072.4:c.1621C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012072.4(CD93):​c.1621C>A​(p.Pro541Thr) 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. 15/22 in silico tools predict 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. P541S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CD93 NM_012072.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 34 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22804564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD93	NM_012072.4	c.1621C>A	p.Pro541Thr	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.1621C>A	p.Pro541Thr	missense_variant	Exon 1 of 2	1	NM_012072.4	ENSP00000246006.4
CD93	ENST00000850633.1	n.1621C>A		non_coding_transcript_exon_variant	Exon 1 of 5			ENSP00000520912.1
CD93	ENST00000850634.1	n.1621C>A		non_coding_transcript_exon_variant	Exon 1 of 3			ENSP00000520913.1
CD93	ENST00000850635.1	n.1621C>A		non_coding_transcript_exon_variant	Exon 1 of 4			ENSP00000520914.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	9.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.6
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.23
Sift	Benign	0.30	T
Sift4G	Benign	0.32	T
Polyphen		0.93	P
Vest4		0.20
MutPred		0.16		Gain of glycosylation at P541 (P = 0.0743);
MVP		0.92
MPC		0.33
ClinPred		0.61	D
GERP RS		3.8
Varity_R		0.042
gMVP		0.39
Mutation Taster		=95/5	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: rs3746731; hg19: chr20-23065209;