rs542742446

Variant names:

• chr3-74285465-C-G
• rs542742446
• NM_020872.3:c.2544G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-74285465-C-G
• chr3-74285465-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020872.3(CNTN3):​c.2544G>C​(p.Lys848Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K848K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNTN3 NM_020872.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17584655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN3	NM_020872.3	c.2544G>C	p.Lys848Asn	missense_variant	Exon 20 of 23	ENST00000263665.7	NP_065923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN3	ENST00000263665.7	c.2544G>C	p.Lys848Asn	missense_variant	Exon 20 of 23	1	NM_020872.3	ENSP00000263665.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248582 Hom.: 0 AF XY: 0.00000744 AC XY: 1 AN XY: 134376

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460108 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726380

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.89
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.88	L
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.0040	B
Vest4		0.22
MutPred		0.38		Loss of ubiquitination at K848 (P = 0.0074);
MVP		0.44
MPC		0.28
ClinPred		0.44	T
GERP RS		-5.2
Varity_R		0.46
gMVP		0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs542742446; hg19: chr3-74334616;