3-74285487-C-T

Variant names:

• chr3-74285487-C-T
• rs199931035
• NM_020872.3:c.2522G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020872.3(CNTN3):​c.2522G>A​(p.Arg841Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,608,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: CNTN3 NM_020872.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.632
• Publications: 3 publications found

Genes affected

CNTN3 (HGNC:2173): (contactin 3) Predicted to be involved in cell adhesion and nervous system development. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009720057).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020872.3. 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
	CNTN3	NM_020872.3	MANE Select	c.2522G>A	p.Arg841Gln	missense	Exon 20 of 23	NP_065923.1	Q9P232
	CNTN3	NM_001393376.1		c.2522G>A	p.Arg841Gln	missense	Exon 20 of 23	NP_001380305.1	Q9P232

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN3	ENST00000263665.7	TSL:1 MANE Select	c.2522G>A	p.Arg841Gln	missense	Exon 20 of 23	ENSP00000263665.6	Q9P232
	CNTN3	ENST00000962150.1		c.2516G>A	p.Arg839Gln	missense	Exon 21 of 24	ENSP00000632209.1
	CNTN3	ENST00000962149.1		c.2207G>A	p.Arg736Gln	missense	Exon 18 of 21	ENSP00000632208.1

Frequencies

GnomAD3 genomes AF: 0.000409 AC: 62 AN: 151744 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000533

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000626

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000961

GnomAD2 exomes AF: 0.000530 AC: 129 AN: 243418 AF XY: 0.000607

Gnomad AFR exome AF: 0.000188

Gnomad AMR exome AF: 0.000549

Gnomad ASJ exome AF: 0.00594

Gnomad EAS exome AF: 0.000113

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000263

Gnomad OTH exome AF: 0.000682

GnomAD4 exome AF: 0.000336 AC: 490 AN: 1456614 Hom.: 0 Cov.: 31 AF XY: 0.000362 AC XY: 262 AN XY: 724588

African (AFR) AF: 0.000332 AC: 11 AN: 33142

American (AMR) AF: 0.000548 AC: 24 AN: 43826

Ashkenazi Jewish (ASJ) AF: 0.00593 AC: 153 AN: 25804

East Asian (EAS) AF: 0.0000509 AC: 2 AN: 39328

South Asian (SAS) AF: 0.000327 AC: 28 AN: 85600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00175 AC: 10 AN: 5726

European-Non Finnish (NFE) AF: 0.000178 AC: 197 AN: 1109710

Other (OTH) AF: 0.00108 AC: 65 AN: 60164

GnomAD4 genome AF: 0.000408 AC: 62 AN: 151862 Hom.: 0 Cov.: 31 AF XY: 0.000445 AC XY: 33 AN XY: 74196

African (AFR) AF: 0.000531 AC: 22 AN: 41436

American (AMR) AF: 0.000131 AC: 2 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5096

South Asian (SAS) AF: 0.000626 AC: 3 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67956

Other (OTH) AF: 0.000951 AC: 2 AN: 2104

Alfa AF: 0.000504 Hom.: 0

Bravo AF: 0.000468

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000420 AC: 51

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.0097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.63
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.29	T
Sift4G	Benign	0.44	T
Polyphen		0.018	B
Vest4		0.25
MVP		0.58
MPC		0.28
ClinPred		0.032	T
GERP RS		4.4
Varity_R		0.097
gMVP		0.42
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs199931035; hg19: chr3-74334638; COSMIC: COSV55167043;