rs375992095

Variant names:

• chr3-74285335-C-A
• rs375992095
• NM_020872.3:c.2674G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-74285335-C-A
• chr3-74285335-C-G
• chr3-74285335-C-T

Variant summary

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

The NM_020872.3(CNTN3):​c.2674G>T​(p.Ala892Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,306 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. A892T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CNTN3 NM_020872.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• Publications: 0 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: 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=0.071768284).

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.2674G>T	p.Ala892Ser	missense	Exon 20 of 23	NP_065923.1	Q9P232
	CNTN3	NM_001393376.1		c.2674G>T	p.Ala892Ser	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.2674G>T	p.Ala892Ser	missense	Exon 20 of 23	ENSP00000263665.6	Q9P232
	CNTN3	ENST00000962150.1		c.2668G>T	p.Ala890Ser	missense	Exon 21 of 24	ENSP00000632209.1
	CNTN3	ENST00000962149.1		c.2359G>T	p.Ala787Ser	missense	Exon 18 of 21	ENSP00000632208.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457306 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725122

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33066

American (AMR) AF: 0.00 AC: 0 AN: 43440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 39446

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110458

Other (OTH) AF: 0.00 AC: 0 AN: 60132

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.82	L
PhyloP100		0.72
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.021
Sift	Benign	0.65	T
Sift4G	Benign	0.49	T
Polyphen		0.0020	B
Vest4		0.22
MutPred		0.22		Loss of glycosylation at S891 (P = 0.0113)
MVP		0.51
MPC		0.30
ClinPred		0.15	T
GERP RS		2.4
Varity_R		0.029
gMVP		0.19
Mutation Taster		=89/11	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: rs375992095; hg19: chr3-74334486;