21-17558991-C-G

Variant names:

• chr21-17558991-C-G
• rs142306071
• NM_001338.5:c.431C>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.431C>G​(p.Ala144Gly) 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. 16/22 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. A144V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CXADR NM_001338.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• 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=0.21733144).

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.431C>G	p.Ala144Gly	missense	Exon 4 of 7	NP_001329.1	P78310-1
	CXADR	NM_001207066.2		c.431C>G	p.Ala144Gly	missense	Exon 4 of 8	NP_001193995.1	P78310-6
	CXADR	NM_001207063.2		c.431C>G	p.Ala144Gly	missense	Exon 4 of 5	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.431C>G	p.Ala144Gly	missense	Exon 4 of 7	ENSP00000284878.7	P78310-1
	CXADR	ENST00000400166.5	TSL:1	c.431C>G	p.Ala144Gly	missense	Exon 4 of 5	ENSP00000383030.1	P78310-5
	CXADR	ENST00000400165.5	TSL:1	c.416-6437C>G		intron	N/A	ENSP00000383029.1	P78310-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248264 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.8
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.27
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.043	D
Polyphen		0.0050	B
Vest4		0.12
MutPred		0.69		Gain of disorder (P = 0.0719)
MVP		0.85
MPC		0.31
ClinPred		0.56	D
GERP RS		0.85
Varity_R		0.31
gMVP		0.65
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: rs142306071; hg19: chr21-18931309;