NM_078481.4:c.643T>A

Variant names:

• chr19-14397675-T-A
• NM_078481.4:c.643T>A

Variant summary

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

The NM_078481.4(ADGRE5):​c.643T>A​(p.Ser215Thr) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: ADGRE5 NM_078481.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0990
• Publications: 0 publications found

Genes affected

ADGRE5 (HGNC:1711): (adhesion G protein-coupled receptor E5) This gene encodes a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors, which mediate cell-cell interactions. These proteins are cleaved by self-catalytic proteolysis into a large extracellular subunit and seven-span transmembrane subunit, which associate at the cell surface as a receptor complex. The encoded protein may play a role in cell adhesion as well as leukocyte recruitment, activation and migration, and contains multiple extracellular EGF-like repeats which mediate binding to chondroitin sulfate and the cell surface complement regulatory protein CD55. Expression of this gene may play a role in the progression of several types of cancer. Alternatively spliced transcript variants encoding multiple isoforms with 3 to 5 EGF-like repeats have been observed for this gene. This gene is found in a cluster with other EGF-TM7 genes on the short arm of chromosome 19. [provided by RefSeq, Jun 2011]

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=0.20155421).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078481.4. 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
	ADGRE5	NM_078481.4	MANE Select	c.643T>A	p.Ser215Thr	missense	Exon 7 of 20	NP_510966.1	P48960-1
	ADGRE5	NM_001025160.3		c.496T>A	p.Ser166Thr	missense	Exon 6 of 19	NP_001020331.1	P48960-3
	ADGRE5	NM_001784.6		c.364T>A	p.Ser122Thr	missense	Exon 5 of 18	NP_001775.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRE5	ENST00000242786.6	TSL:1 MANE Select	c.643T>A	p.Ser215Thr	missense	Exon 7 of 20	ENSP00000242786.4	P48960-1
	ADGRE5	ENST00000357355.7	TSL:1	c.496T>A	p.Ser166Thr	missense	Exon 6 of 19	ENSP00000349918.2	P48960-3
	ADGRE5	ENST00000358600.7	TSL:1	c.364T>A	p.Ser122Thr	missense	Exon 5 of 18	ENSP00000351413.2	P48960-2

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 20

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.3
DANN	Benign	0.91
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.47	T
PhyloP100		0.099
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Sift	Benign	0.20	T
Sift4G	Benign	0.39	T
Vest4		0.21
MutPred		0.53		Gain of catalytic residue at S215 (P = 0.0216)
MVP		0.58
MPC		1.8
ClinPred		0.069	T
GERP RS		-1.7
gMVP		0.51
Mutation Taster		=98/2	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

hg19: chr19-14508487;