chr17-42683904-A-G

Variant names:

• chr17-42683904-A-G
• rs2271029
• NM_003632.3:c.151A>G

Variant summary

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

The NM_003632.3(CNTNAP1):​c.151A>G​(p.Arg51Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R51R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CNTNAP1 NM_003632.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 36 publications found

Genes affected

CNTNAP1 (HGNC:8011): (contactin associated protein 1) The gene product was initially identified as a 190-kD protein associated with the contactin-PTPRZ1 complex. The 1,384-amino acid protein, also designated p190 or CASPR for 'contactin-associated protein,' includes an extracellular domain with several putative protein-protein interaction domains, a putative transmembrane domain, and a 74-amino acid cytoplasmic domain. Northern blot analysis showed that the gene is transcribed predominantly in brain as a transcript of 6.2 kb, with weak expression in several other tissues tested. The architecture of its extracellular domain is similar to that of neurexins, and this protein may be the signaling subunit of contactin, enabling recruitment and activation of intracellular signaling pathways in neurons. [provided by RefSeq, Jan 2009]

CCR10 (HGNC:4474): (C-C motif chemokine receptor 10) Chemokines are a group of small (approximately 8 to 14 kD), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane, G protein-coupled receptors. Chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. Chemokines are divided into 2 major subfamilies, CXC and CC, based on the arrangement of the first 2 of the 4 conserved cysteine residues; the 2 cysteines are separated by a single amino acid in CXC chemokines and are adjacent in CC chemokines. CCR10 is the receptor for CCL27 (SCYA27; MIM 604833); CCR10-CCL27 interactions are involved in T cell-mediated skin inflammation (Homey et al., 2002 [PubMed 11821900]).[supplied by OMIM, Mar 2008]

ENSG00000267765 (HGNC:58591):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003632.3. 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
	CNTNAP1	NM_003632.3	MANE Select	c.151A>G	p.Arg51Gly	missense	Exon 2 of 24	NP_003623.1	P78357

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP1	ENST00000264638.9	TSL:1 MANE Select	c.151A>G	p.Arg51Gly	missense	Exon 2 of 24	ENSP00000264638.3	P78357
	CNTNAP1	ENST00000591662.1	TSL:1	n.151A>G		non_coding_transcript_exon	Exon 2 of 24	ENSP00000466571.1	K7EMM9
	CCR10	ENST00000591568.1	TSL:3	c.-731T>C		5_prime_UTR	Exon 1 of 2	ENSP00000467331.1	K7EPC9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 44319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	17
DANN	Benign	0.57
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	0.18	N
PhyloP100		2.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	2.4	N
REVEL	Uncertain	0.54
Sift	Benign	1.0	T
Sift4G	Benign	0.18	T
Polyphen		0.68	P
Vest4		0.48
MutPred		0.64		Loss of methylation at R51 (P = 0.038)
MVP		0.75
MPC		1.4
ClinPred		0.42	T
GERP RS		4.8
PromoterAI		0.048	Neutral
Varity_R		0.18
gMVP		0.76

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: rs2271029; hg19: chr17-40835922;