21-17561406-C-G

Variant names:

• chr21-17561406-C-G
• rs767607873
• NM_001338.5:c.763C>G

Variant summary

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

The NM_001338.5(CXADR):​c.763C>G​(p.Leu255Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. L255F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CXADR NM_001338.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• Publications: 0 publications found

Genes affected

CXADR (HGNC:2559): (CXADR Ig-like cell adhesion molecule) The protein encoded by this gene is a type I membrane receptor for group B coxsackieviruses and subgroup C adenoviruses. Several transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene are found on chromosomes 15, 18, and 21. [provided by RefSeq, May 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=0.12498605).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001338.5. 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
	CXADR	NM_001338.5	MANE Select	c.763C>G	p.Leu255Val	missense	Exon 6 of 7	NP_001329.1	P78310-1
	CXADR	NM_001207066.2		c.763C>G	p.Leu255Val	missense	Exon 6 of 8	NP_001193995.1	P78310-6
	CXADR	NM_001207063.2		c.571+2275C>G		intron	N/A	NP_001193992.1	P78310-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXADR	ENST00000284878.12	TSL:1 MANE Select	c.763C>G	p.Leu255Val	missense	Exon 6 of 7	ENSP00000284878.7	P78310-1
	CXADR	ENST00000400166.5	TSL:1	c.571+2275C>G		intron	N/A	ENSP00000383030.1	P78310-5
	CXADR	ENST00000400165.5	TSL:1	c.416-4022C>G		intron	N/A	ENSP00000383029.1	P78310-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249488 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460044 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726326

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5620

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111008

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.2
DANN	Benign	0.96
DEOGEN2	Benign	0.33	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.55
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.10
Sift	Uncertain	0.021	D
Sift4G	Benign	0.25	T
Polyphen		0.0030	B
Vest4		0.26
MutPred		0.47		Loss of stability (P = 0.0404)
MVP		0.57
MPC		0.045
ClinPred		0.030	T
GERP RS		-1.9
Varity_R		0.047
gMVP		0.49
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: rs767607873; hg19: chr21-18933724;