3-74264411-A-G

Variant names:

• chr3-74264411-A-G
• rs946118509
• NM_020872.3:c.3077T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020872.3(CNTN3):​c.3077T>C​(p.Val1026Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,581,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: CNTN3 NM_020872.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.72
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062051654).
• BP6: Variant 3-74264411-A-G is Benign according to our data. Variant chr3-74264411-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2597168.Status of the report is criteria_provided_single_submitter, 1 stars.

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.3077T>C	p.Val1026Ala	missense	Exon 23 of 23	NP_065923.1	Q9P232
	CNTN3	NM_001393376.1		c.3077T>C	p.Val1026Ala	missense	Exon 23 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.3077T>C	p.Val1026Ala	missense	Exon 23 of 23	ENSP00000263665.6	Q9P232
	CNTN3	ENST00000962150.1		c.3071T>C	p.Val1024Ala	missense	Exon 24 of 24	ENSP00000632209.1
	CNTN3	ENST00000962149.1		c.2762T>C	p.Val921Ala	missense	Exon 21 of 21	ENSP00000632208.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000423 AC: 1 AN: 236340 AF XY: 0.00000783

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000582

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000840 AC: 12 AN: 1428890 Hom.: 0 Cov.: 26 AF XY: 0.00000844 AC XY: 6 AN XY: 711218

African (AFR) AF: 0.00 AC: 0 AN: 32194

American (AMR) AF: 0.00 AC: 0 AN: 41462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25290

East Asian (EAS) AF: 0.0000515 AC: 2 AN: 38816

South Asian (SAS) AF: 0.0000488 AC: 4 AN: 81994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1091308

Other (OTH) AF: 0.0000675 AC: 4 AN: 59228

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152238 Hom.: 1 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74428

African (AFR) AF: 0.0000241 AC: 1 AN: 41554

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.73
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.81	N
PhyloP100		1.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.82	N
REVEL	Benign	0.095
Sift	Benign	0.51	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.065
MutPred		0.46		Loss of stability (P = 0.0567)
MVP		0.53
MPC		0.28
ClinPred		0.066	T
GERP RS		5.0
Varity_R		0.035
gMVP		0.34
Mutation Taster		=96/4	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: rs946118509; hg19: chr3-74313562;